Systems for delivering implaintable devices across an atrial septum

ABSTRACT

Systems for delivering a device for regulating blood pressure across a patients atrial septum are provided. The delivery apparatus may include a first catheter, a hub having one or more engagers disposed thereon, the one or more engagers configured to releasably engage with a first expandable end of the shunt in a contracted delivery state within a lumen of a sheath, and an second catheter extending through a center lumen of the first catheter and the hub, wherein the first catheter, the hub, and the second catheter are independently moveable relative to the sheath. The inventive devices may reduce left atrial pressure and left ventricular end diastolic pressure, increase cardiac output, increase ejection fraction, relieve pulmonary congestion, and lower pulmonary artery pressure, among other benefits. The inventive devices also may be used to treat subjects having heart failure, pulmonary congestion, or myocardial infarction, among other pathologies.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of U.S. patentapplication Ser. No. 16/374,698, filed Apr. 3, 2019, the entire contentsof which are incorporated herein by reference.

FIELD OF THE INVENTION

This application generally relates to devices and methods for deliveringimplantable devices to the atrial septum, particularly in subjects withheart pathologies such as pulmonary arterial hypertension (PAH),congestive heart failure (CHF) or myocardial infarction (MI).

BACKGROUND OF THE INVENTION

Pulmonary arterial hypertension occurs when the pressure within theblood vessels and lungs becomes too high. PAH may be caused byobstruction in the arties in the lung such as the development of scartissue in the blood vessels of the lungs, but in many cases, the causeis unknown. Under normal conditions, the pressure within the right sideof the heart and the blood vessels of the lungs is lower than the restof the body which maximizes oxygenation of the blood in the lungs. WithPAH, the heart must work harder under greater pressure to pump bloodthrough the arteries in the lungs, weakening the heart muscles overtime. As a result, the heart may be unable to sufficiently pump blood tothe lungs to be oxygenated to keep the body functioning normally.

Heart failure is the physiological state in which cardiac output isinsufficient to meet the needs of the body or to do so only at a higherfilling pressure. There are many underlying causes of HF, includingmyocardial infarction, coronary artery disease, valvular disease,hypertension, and myocarditis. Chronic heart failure is associated withneurohormonal activation and alterations in autonomic control. Althoughthese compensatory neurohormonal mechanisms provide valuable support forthe heart under normal physiological circumstances, they also play afundamental role in the development and subsequent progression of HF.

For example, one of the body's main compensatory mechanisms for reducedblood flow in HF is to increase the amount of salt and water retained bythe kidneys. Retaining salt and water, instead of excreting it viaurine, increases the volume of blood in the bloodstream and helps tomaintain blood pressure. However, the larger volumes of blood also causethe heart muscle, particularly the ventricles, to become enlarged. Asthe heart chambers become enlarged, the wall thickness decreases and theheart's contractions weaken, causing a downward spiral in cardiacfunction. Another compensatory mechanism is vasoconstriction of thearterial system, which raises the blood pressure to help maintainadequate perfusion, thus increasing the load that the heart must pumpagainst.

In low ejection fraction (EF) heart failure, high pressures in the heartresult from the body's attempt to maintain the high pressures needed foradequate peripheral perfusion. However, as the heart weakens as a resultof such high pressures, the disorder becomes exacerbated. Pressure inthe left atrium may exceed 25 mmHg, at which stage fluids from the bloodflowing through the pulmonary circulatory system transudate or flow outof the pulmonary capillaries into the pulmonary interstitial spaces andinto the alveoli, causing lung congestion and, if untreated, thesyndrome of acute pulmonary edema and death.

Table 1 lists typical ranges of right atrial pressure (RAP), rightventricular pressure (RVP), left atrial pressure (LAP), left ventricularpressure (LVP), cardiac output (CO), and stroke volume (SV) for a normalheart and for a heart suffering from HF. In a normal heart beating ataround 70 beats/minute, the stroke volume needed to maintain normalcardiac output is about 60 to 100 milliliters. When the preload,after-load, and contractility of the heart are normal, the pressuresrequired to achieve normal cardiac output are listed in Table 1. In aheart suffering from HF, the hemodynamic parameters change (as shown inTable 1) to maintain peripheral perfusion.

TABLE 1 Parameter Normal Range HF Range RAP (mmHg) 2-6  6-20 RVSP (mmHg)15-25 20-80 LAP (mmHg)  6-12 15-50 LVEDP (mmHg)  6-12 15-50 CO(liters/minute) 4-8 2-6 SV (milliliters/beat)  60-100 30-80

HF is generally classified as either systolic heart failure (SHF) ordiastolic heart failure (DHF). In SHF, the pumping action of the heartis reduced or weakened. A common clinical measurement is the ejectionfraction, which is a function of the blood ejected out of the leftventricle (stroke volume) divided by the maximum volume in the leftventricle at the end of diastole or relaxation phase. A normal ejectionfraction is greater than 50%. Systolic heart failure generally causes adecreased ejection fraction of less than 40%. Such patients have heartfailure with reduced ejection fraction (HFrEF). A patient with HFrEF mayusually have a larger left ventricle because of a phenomenon called“cardiac remodeling” that occurs secondary to the higher ventricularpressures.

In DHF, the heart generally contracts normally, with a normal ejectionfraction, but is stiffer, or less compliant, than a healthy heart wouldbe when relaxing and filling with blood. Such patients are said to haveheart failure with preserved ejection fraction (HFpEF). This stiffnessmay impede blood from filling the heart and produce backup into thelungs, which may result in pulmonary venous hypertension and lung edema.HFpEF is more common in patients older than 75 years, especially inwomen with high blood pressure.

Both variants of HF have been treated using pharmacological approaches,which typically involve the use of vasodilators for reducing theworkload of the heart by reducing systemic vascular resistance, as wellas diuretics, which inhibit fluid accumulation and edema formation, andreduce cardiac filling pressure. No pharmacological therapies have beenshown to improve morbidity or mortality in HFpEF whereas several classesof drugs have made an important impact on the management of patientswith HFrEF, including renin-angiotensin antagonists, beta blockers, andmineralocorticoid antagonists. Nonetheless, in general, HF remains aprogressive disease and most patients have deteriorating cardiacfunction and symptoms over time. In the U.S., there are over 1 millionhospitalizations annually for acutely worsening HF and mortality ishigher than for most forms of cancer.

In more severe cases of HFrEF, assist devices such as mechanical pumpsare used to reduce the load on the heart by performing all or part ofthe pumping function normally done by the heart. Chronic leftventricular assist devices (LVAD), and cardiac transplantation, oftenare used as measures of last resort. However, such assist devicestypically are intended to improve the pumping capacity of the heart, toincrease cardiac output to levels compatible with normal life, and tosustain the patient until a donor heart for transplantation becomesavailable. Such mechanical devices enable propulsion of significantvolumes of blood (liters/min), but are limited by a need for a powersupply, relatively large pumps, and pose a risk of hemolysis, thrombusformation, and infection. Temporary assist devices, intra-aorticballoons, and pacing devices have also been used.

Various devices have been developed using stents to modify bloodpressure and flow within a given vessel, or between chambers of theheart Implantable interatrial shunt devices have been successfully usedin patients with severe symptomatic heart failure. By diverting orshunting blood from the left atrium (LA) to the right atrium (RA), thepressure in the left atrium is lowered or prevented from elevating ashigh as it would otherwise (left atrial decompression). Such anaccomplishment would be expected to prevent, relieve, or limit thesymptoms, signs, and syndromes associated of pulmonary congestion. Theseinclude severe shortness of breath, pulmonary edema, hypoxia, the needfor acute hospitalization, mechanical ventilation, and death.

Percutaneous implantation of interatrial shunts generally requirestransseptal catheterization immediately preceding shunt deviceinsertion. The transseptal catheterization system is placed from anentrance site in the femoral vein, across the interatrial septum in theregion of fossa ovalis (FO), which is the central and thinnest region ofthe interatrial septum. The FO in adults is typically 15-20 mm in itsmajor axis dimension and <3 mm in thickness, but in certaincircumstances may be up to 10 mm thick. LA chamber access may beachieved using a host of different techniques familiar to those skilledin the art, including but not limited to: needle puncture, styletpuncture, screw needle puncture, and radiofrequency ablation. Thepassageway between the two atria is dilated to facilitate passage of ashunt device having a desired orifice size. Dilation generally isaccomplished by advancing a tapered sheath/dilator catheter system orinflation of an angioplasty type balloon across the FO. This is the samegeneral location where a congenital secundum atrial septal defect (ASD)would be located.

Moreover, devices such as those described in U.S. Pat. No. 5,312,341 toTuri, have been theorized for transseptal catheterization. Specifically,these devices have a retaining means such as an inflatable balloon thatis inflated within the left atrium of the patient to prevent inadvertentretraction of the distal tip of the sheath from the left atrium duringsubsequent portions of the catheterization procedure.

In view of the foregoing, it would be desirable to provide devices fordelivering implantable devices to the atrial septum of the heart toreduce left atrial pressure.

It would further be desirable to provide devices and methods forcontrolled positioning and delivery of atrial shunt devices.

SUMMARY OF THE INVENTION

The present invention overcomes the drawbacks of previously-knowndevices by providing apparatus for delivering a device for regulatingblood pressure between a patient's left atrium and right atrium. Thedelivery apparatus includes a sheath having a distal region sized andshaped for percutaneous advancement to the atrial septum, a proximalregion, and a sheath lumen extending therethrough, the sheath lumensized and shaped to receive the shunt in a contracted delivery state.The apparatus also includes a first, outer catheter moveably disposedwithin the sheath lumen, wherein the first catheter has a first catheterlumen extending therethrough, and a hub moveably disposed within thesheath lumen distal to the first catheter.

The hub has a hub lumen extending therethrough and one or more engagerssized and shaped to releaseably engage the shunt in the contracteddelivery state within the sheath lumen. The hub may include anengagement portion and a ring portion, wherein the engagement portion ofthe hub has a diameter smaller than a diameter of the ring portion, andwherein the one or more engagers are disposed circumferentially aroundthe engagement portion of the hub. For example, a first expandable endof the shunt may be positioned between the one or more engagers and thering portion and between an outer surface of the engagement portion andan inner wall of the sheath in the contracted delivery state within thesheath lumen. The hub further may include a proximal portion, such thatthe first catheter has a cavity sized and shaped to receive at least aportion of the proximal portion to limit movement of the hub relative tothe first catheter.

In addition, the apparatus further includes a second, inner cathetermoveably disposed within the first catheter lumen and the hub lumen, andwherein the first catheter and the hub are movable which the secondcatheter remains in place. The second catheter may include a stop, e.g.,a lock ring, disposed at a distal end of the second catheter, such thatthe hub has a cavity sized and shaped to receive at least a portion ofthe stop to limit movement of the hub relative to the second catheter.In addition, the second catheter may include a guidewire lumen extendingtherethrough sized and shaped to receive a guidewire.

The apparatus also includes a handle disposed at the proximal region ofthe sheath. The first catheter, the hub, and the second catheter areindependently movable relative to the sheath responsive to actuation atthe handle to facilitate transition of the shunt from the contracteddelivery state to an expanded deployed state at the atrial septum. Inaddition, the handle includes a knob that when actuated facilitatesdeployment of and/or halfway retrieval of the shunt at the atrial septumby adjusting a length of the delivery apparatus relative to the sheath.For example, the knob may be actuated to gradually adjust the length ofthe delivery apparatus relative to the sheath to assist in halfwayretrieval of the shunt.

The handle may include a first actuator, the first actuator coupled tothe sheath such that actuation of the first actuator causes the sheathto move relative to the hub, the first catheter, and the secondcatheter. The handle also may include a second actuator, the secondactuator coupled to the second catheter such that actuation of thesecond actuator causes the second catheter to move relative to thesheath, the hub, and the first catheter. For example, the secondactuator may be coupled to the second catheter via one or moreguiderails and a pusher plate. Accordingly, the first actuator may movealong the one or more guiderails within a housing of the handle.

The apparatus also includes a locking mechanism for releasably couplingthe hub and the first catheter. Thus, the handle further includes athird actuator operatively coupled to the locking mechanism such thatactuation of the third actuator causes the locking mechanism to coupleor decouple the hub and the first catheter. The handle further mayinclude an actuation ring positioned between the second actuator and thethird actuator, wherein the actuation ring has an indented distal edgesized and shaped to engage with a toothed proximal edge of the thirdactuator, and a grooved proximal edge sized and shaped to engage with anindented distal edge of the second actuator. For example, actuation ofthe third actuator may orient the actuation ring such that actuation ofthe second actuator is inhibited.

In accordance with another aspect of the invention, a method fordelivering a shunt at an atrial septum of a patient is provided. Themethod includes selecting a sheath and a delivery apparatus including afirst, outer catheter, a hub distal to and releasably coupled to thefirst catheter, the hub having one or more engagers disposed thereon,the one or more engagers sized and shaped to releasably engage with theshunt in a contracted delivery state within a lumen of the sheath, and asecond, inner catheter extending through a center lumen of the firstcatheter and the hub. The first catheter, the hub, and the secondcatheter are independently moveable relative to the sheath uponactuation of a handle operatively coupled to the sheath and the deliveryapparatus.

The method further includes advancing a distal end of the sheath throughthe atrial septum into a first atrium, and then advancing the deliveryapparatus within the lumen of the sheath, and actuating the handle tomove the delivery apparatus distally relative to the sheath such that afirst expandable end of the shunt extends distally out the distal end ofthe sheath and transitions from a contracted state within the lumen ofthe sheath to an expanded state in the first atrium. The method thenincludes (1) actuating the handle to move the second catheter distallyrelative to the sheath, the first catheter, and the hub; (2) moving thedelivery apparatus and the sheath proximally until the first expandableend of the shunt rests against the atrial septum from within the firstatrium; and (3) actuating the handle to decouple the hub and the firstcatheter. The method further includes moving the first catheter and thesheath proximally relative to the hub to disengage a second expandableend of the shunt with the one or more engagers of the hub and expose thesecond expandable end of the shunt from the sheath to transition fromthe contracted state within the lumen of the sheath to an expanded statein a second atrium. Finally, the method includes removing the sheath andthe delivery apparatus from the patient such that a neck region of theshunt is positioned within the atrial septum to permit blood to flowthrough an opening in the neck region of the shunt and thereby throughthe atrial septum.

In accordance with one aspect of the invention, the method furtherincludes actuating the handle to adjust a length of the deliveryapparatus relative to a length of the sheath prior to disengaging thesecond expandable end of the shunt with the one or more engagers of thehub to assist in halfway retrieval of the shunt. For example, the handlemay be actuated to gradually adjust the length of the delivery apparatusrelative to the length of the sheath to facilitate retrieving the shuntin a partially deployed state. In accordance with yet another aspect ofthe invention, the second catheter includes a guidewire lumen extendingtherethrough sized and shaped to receive a guidewire, such that themethod also includes inserting a guidewire percutaneously through theatrial septum into the first atrium. Thus, advancing the deliveryapparatus through the sheath includes advancing the delivery apparatusover the guidewire. As will be understood by a person ordinarily skilledin the art, a dilator may be advanced over the guidewire through thefossa ovalis to enlarge the opening within the atrial septum, andremoved prior to advancing the sheath and the delivery apparatus withinthe lumen of the sheath over the guidewire.

In accordance with another aspect of the present invention, a system forretrieving a shunt implanted in an atrial septum of a patient isprovided. The system includes a sheath having a proximal end, a distalend, and a lumen extending therebetween. The system further includes oneor more grappling hooks slidably movable through the lumen of thesheath. The one or more grappling hooks are transitionable between acontracted delivery state within the lumen of the sheath and an expandeddeployed state when exposed from the distal end of the sheath. Inaddition, the one or more grappling hooks each have a hook portion thatmay be coupled to a proximal end of the shunt in the expanded deployedstate. Accordingly, when the one or more grappling hooks are coupled tothe shunt, transition of the one or more grappling hooks from theexpanded deployed state to the contracted delivery state causes theproximal end of the shunt to transition from an expanded deployed stateto a collapsed retrieval state. Moreover, the sheath is sized and shapedto receive the proximal end of the shunt in the collapsed retrievalstate and may be moved over the shunt to transition a distal end of theshunt from an expanded deployed state to a collapsed retrieval state, tothereby retrieve the shunt from the atrial septum.

In one embodiment, the one or more grappling hooks are biased toward theexpanded deployed state. Accordingly, the system further may include arestraint slidably movable over the one or more grappling hooks totransition the one or more grappling hooks between the contracteddelivery state and the expanded deployed state. For example, the one ormore grappling hooks may have a non-expandable catheter portion proximalto the hook portion, such that movement of the restraint towards thenon-expandable catheter portion causes the one or more grappling hooksto transition from the contracted delivery state to the expandeddeployed state, and movement of the restraint towards the hook portioncauses the one or more grappling hooks to transition from the expandeddeployed state to the contracted delivery state.

In another embodiment, the one or more grappling hooks are biased towardthe contracted delivery state. Accordingly, the system further mayinclude a balloon catheter slidably movable within the lumen of thesheath. The balloon catheter includes a balloon transitionable from adeflated state to an inflated state adjacent the proximal end of theshunt, thereby creating a ramp in the inflated state such that movementof the one or more grappling hooks over the balloon in the inflatedstate causes the one or more grappling hooks to transition from thecontracted delivery state to the expanded deployed state.

In accordance with another aspect of the present invention, a system forloading a shunt for intravascular delivery to an atrial septum of apatient is provided. The system may include a proximal loader havingproximal end, a distal end, and a lumen extending therebetween. Forexample, a proximal portion of the lumen may be sized and shaped toreceive a proximal end of the shunt in a collapsed delivery state, and adistal portion of the lumen may be sized and shaped to transition theproximal end of the shunt from an expanded deployed state to thecollapsed delivery state when the proximal end of the shunt is receivedthrough the distal portion of the lumen. In addition, the system furthermay include a distal loader having a cavity sized and shaped to receivethe proximal loader therein. For example, movement of the proximalloader distally within the cavity of the distal loader may cause theproximal end of the shunt positioned within the cavity of the distalloader to transition from the expanded deployed state to the collapseddelivery state within the proximal portion of the lumen of the proximalloader. Moreover, the proximal portion of the lumen further may be sizedand shaped to slidably receive a delivery apparatus therethrough, suchthat the delivery apparatus may engage with the proximal end of theshunt in the collapsed delivery state.

In accordance with yet another aspect of the present invention, analternative method for delivering a shunt to an atrial septum of apatient is provided. For example, the method may include: advancing adistal end of a sheath having a cap removably disposed thereon from afirst atrium, through the atrial septum into a second atrium, the sheathhaving a shunt disposed therein in a collapsed delivery state, the shuntcoupled to a delivery apparatus within the sheath; decoupling the capfrom the distal end of the sheath; retracting the sheath relative to thecap and the shunt to partially deploy the shunt within the secondatrium; moving the sheath and the shunt together proximally to align aradiopaque marker disposed on the distal end of the sheath with theatrial septum; decoupling the shunt from the delivery apparatus;retracting the sheath until the shunt is fully deployed within theatrial septum; and removing the sheath and delivery apparatus from thepatient. The method further may include advancing the sheath distallyprior to decoupling the shunt from the delivery apparatus to transitionthe partially deployed shunt to the collapsed delivery state within thesheath, e.g., for half-way retrieval of the shunt.

In accordance with another aspect of the present invention, a guidewireloading device for loading a guidewire into an atrial shunt deliverycartridge, e.g., a cartridge for loading a shunt for intravasculardelivery to the atrial septum of a patient, is provided. The loadingdevice may include a proximal portion having a lumen sized and shaped toreceive the atrial shunt delivery cartridge therein and a distal portionhaving an adjustable lumen. In addition, the loading device may includea pair of flexible wings extending radially from the distal portion. Thepair of flexible wings, when a force is applied thereon, may cause adiameter of the adjustable lumen of the distal portion to increase to asize sufficient to receive the atrial shunt delivery cartridge therein.For example, the diameter of the adjustable lumen of the distal portionmay be biased toward a size smaller than when the force is applied onthe pair of flexible wings. Thus, upon release of the force on the pairof flexible wings, the adjustable lumen of the distal portion willsqueeze against the atrial shunt delivery cartridge, thereby holding thecartridge in position to receive the guidewire. Moreover, a free end ofthe pair of flexible wings may include a flat edge extending parallel toa longitudinal axis of the distal portion.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B illustrate an exemplary apparatus for delivering devicesin accordance with the present invention, wherein the exemplaryapparatus is in the engaged position in FIG. 1A and the disengagedposition in FIG. 1B.

FIGS. 2A and 2B, respectively, illustrate the distal end of theexemplary apparatus in the engaged position shown in FIG. 1A and thedisengaged position shown in FIG. 1B.

FIGS. 3A to 3D illustrate the inner components at the distal end of theexemplary apparatus, wherein FIGS. 3A and 3C show the components in theengaged position and FIGS. 3B and 3D show the components in thedisengaged position.

FIG. 4A illustrates the distal end of an exemplary delivery apparatusengaged to an exemplary shunt device, partially shown, in accordancewith the present invention and FIG. 4B illustrates the exemplarydelivery apparatus disengaged from the exemplary shunt device.

FIG. 5 is a flow chart of steps in a method of percutaneously implantingan hourglass-shaped shunt device in a puncture through the fossa ovalisusing the exemplary delivery apparatus, according to some embodiments ofthe present invention.

FIGS. 6A-6Q schematically illustrate steps taken during the method ofFIG. 5, according to some embodiments of the present invention.

FIG. 7A illustrates a proximal end of an alternative exemplary apparatusfor delivering devices in accordance with the present invention, andFIG. 7B illustrates a cross-sectional view of the apparatus of FIG. 7A.

FIGS. 8A and 8B, respectively, illustrate the distal end of thealternative exemplary apparatus of FIGS. 7A and 7B in an engagedposition and a disengaged position.

FIG. 8C illustrates the hook portion of the distal end of thealternative exemplary apparatus of FIGS. 8A and 8B.

FIGS. 9A to 9D illustrate the inner components at the distal end of thealternative exemplary apparatus of FIGS. 8A and 8B, wherein FIGS. 9A and9C show the components in the engaged position and FIGS. 9B and 9D showthe components in the disengaged position.

FIG. 10A illustrates the distal end of the alternative exemplaryapparatus of FIGS. 8A and 8B engaged to an exemplary device, partiallyshown, in accordance with the present invention and FIG. 10B illustratesthe alternative exemplary apparatus disengaged from the exemplarydevice.

FIG. 11 is a flow chart of steps in an exemplary method ofpercutaneously implanting an hourglass-shaped device in a puncturethrough the fossa ovalis using the alternative exemplary apparatus ofFIGS. 7A and 7B, according to some embodiments of the present invention.

FIGS. 12A to 12C illustrate the knob system at the proximal end of thealternative exemplary apparatus of FIGS. 7A and 7B in accordance withthe present invention.

FIG. 13A illustrates an alternative embodiment of the distal end of thedelivery apparatus constructed in accordance with the principles of thepresent invention, wherein the engagement mechanism for coupling thedelivery system to the shunt is embedded within a tube to better ensurethe disengagement of the shunt from the engagement hooks following itsdeployment.

FIGS. 13B to 13D illustrates another alternative exemplary embodiment ofthe distal end of the delivery apparatus constructed in accordance withthe principles of the present invention, wherein the engagementmechanism for coupling the delivery system to the shunt is embeddedwithin a cap to better ensure the disengagement of the shunt from theengagement hooks following its deployment.

FIG. 14 illustrates yet another alternative exemplary apparatus fordelivering devices in accordance with the present invention.

FIG. 15 is a flow chart of steps in an exemplary method ofpercutaneously implanting an hourglass-shaped device in a puncturethrough the fossa ovalis using the alternative exemplary apparatus ofFIG. 14, according to some embodiments of the present invention.

FIGS. 16A-16T schematically illustrate steps taken during the method ofFIG. 15, according to some embodiments of the present invention.

FIG. 17 is a flow chart of steps in an exemplary method of retrieving anhourglass-shaped device implanted in a puncture through the fossa ovalisin accordance with the present invention.

FIGS. 18A-18F schematically illustrate steps taken during the method ofFIG. 17, according to some embodiments of the present invention.

FIG. 19 is a flow chart of steps in an alternative exemplary method ofretrieving an hourglass-shaped device implanted in a puncture throughthe fossa ovalis in accordance with the present invention.

FIGS. 20A-20G schematically illustrate steps taken during the method ofFIG. 19, according to some embodiments of the present invention.

FIG. 21A illustrates yet another alternative exemplary apparatus fordelivering devices in accordance with the present invention, and FIG.21B illustrates the distal end of the apparatus of FIG. 21A.

FIG. 22 illustrates a loading tool for loading an exemplary shunt deviceinto the apparatus of FIG. 21A.

FIG. 23 is a flow chart of steps in a method of using the loading toolof FIG. 22 to load an exemplary shunt device into the apparatus of FIG.21A.

FIGS. 24A-24F illustrates steps taken during the method of FIG. 23,according to some embodiments of the present invention.

FIG. 25A illustrates the distal end of the apparatus of FIG. 21A havingan exemplary shunt device loaded therein, and FIGS. 25B-25C illustratethe inner components of the distal end of the apparatus of FIG. 25A.

FIG. 26A illustrates a proximal end of the apparatus of FIG. 21A fordelivering devices in accordance with the present invention, and FIG.26B illustrates a cross-sectional view of the apparatus of FIG. 26A.

FIG. 27 is a flow chart of steps in an exemplary method ofpercutaneously implanting and halfway-retrieval of an hourglass-shapeddevice in a puncture through the fossa ovalis using the alternativeexemplary apparatus of FIG. 21A, according to some embodiments of thepresent invention.

FIGS. 28A-28I schematically illustrate steps taken during the method ofFIG. 27, according to some embodiments of the present invention.

FIGS. 29A-29D illustrate a guidewire loading tool constructed inaccordance with the principles of the present invention.

FIGS. 30A-30E illustrates a method of using the guidewire loading toolof FIGS. 29A-29D.

FIGS. 31A and 31B are a flow chart of steps in another exemplary methodof percutaneously implanting an hourglass-shaped device in a puncturethrough the fossa ovalis in accordance with the principles of thepresent invention.

FIGS. 32A-32K schematically illustrate steps taken during the method ofFIGS. 31A and 31B, according to some embodiments of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention are directed to devices fordelivering implantable devices to the atrial septum of the heart, andthus may be useful in treating subjects suffering from heart failure orother disorders associated with elevated left atrial pressure. Forexample, the inventive device may be designed to deliver an hourglass or“diabolo” shaped stent, preferably formed of a shape memory metal asdescribed in U.S. Pat. No. 9,629,715 to Nitzan, assigned to the assigneeof the present invention, the entire contents of which are incorporatedherein by reference. The delivery device is configured to lodge thestent securely in the atrial septum, preferably the fossa ovalis, tofunction as an interatrial shunt, allowing blood flow from the leftatrium to the right atrium.

Referring to FIGS. 1A and 1B, apparatus 100 is provided for deliveringinteratrial shunt devices, e.g., devices described in U.S. Pat. No.9,629,715 to Nitzan and U.S. Pat. No. 9,713,696 to Yacoby, assigned tothe assignee of the present invention, the entire contents of each ofwhich are incorporated herein by reference. Apparatus 100 may includedistal end 102, catheter 104, and proximal end 106 having handle 108.Distal end 102 comprises components suitable for coupling apparatus 100to devices of the present invention, as described in detail below.Catheter 104 comprises a biocompatible tube shaft of suitable size,e.g., approximately 14 Fr., and suitable length, e.g., approximately75-100 cm and preferably 85 cm. Proximal end 106 comprises handle 108that is configured to be manipulated, e.g., by a human hand, totransition components in distal end 102 from an engaged position shownin FIG. 1A to a disengaged position shown in FIG. 1B. Handle 108 may bemanipulated, for example, by moving finger grips 110 proximally from alocked position shown in FIG. 1A to an unlocked position shown in FIG.1B. In addition, handle 108 may be manipulated by moving finger grips110 distally from the locked position to the unlocked position so as totransition components in distal end 102 from the disengaged position tothe engaged position to load devices of the present invention.

FIGS. 2A and 2B illustrate distal end 102 in the engaged position ofFIG. 1A and the disengaged position of FIG. 1B, respectively. At distalend 102, apparatus 100 may include latching legs 112, 114, and 116having hook portions 118, 120, and 122, respectively. Latching legs 112,114, and 116 comprise a biocompatible material such as a biocompatiblemetal or polymer, and are positioned longitudinally and radially so asto firmly secure devices of the present invention for delivery. Hookportions 118, 120, and 122 extend outwardly from the distal end oflatching legs 112, 114, and 116, respectively, and are configured to fitsecurely between struts and rings of the devices of the presentinvention. Preferably, hook portions 118, 120, and 122 hook outwardlyaway from center axis 123 of catheter 104 in both the engaged anddisengaged positions as shown in FIGS. 1A and 1B. Center axis 123 iscentered relative to catheter 104 on both a longitudinal andcross-sectional basis. By facing outwardly from center axis 123, hookportions 118, 120, and 122 may engage the inner surface of the device,e.g., within a lumen of a shunt. In one embodiment, hook portions 118,120, and 122 hook generally perpendicularly away from center axis 123from a radial perspective. As will be readily understood by one ofordinary skill in the art, while three latching legs are illustrated,more or fewer latching legs may be used without departing from the scopeof the present invention. For example, one, two, four, five, six, ormore latching legs may be used. Catheter 104 may include cover tube 124which may have a larger diameter than the remaining shaft of catheter104. Cover tube 124 comprises a biocompatible material such as abiocompatible metal or polymer, and may be the same or differentmaterial than the remaining shaft of catheter 104. Components at distalend 102, such as latching legs 112, 114, and 116, may be at leastpartially disposed within cover tube 124. For example, the proximal endsof latching legs 112, 114, and 116 may be coupled to annular member 148and cover tube 124 by laser welding.

Referring now to FIGS. 3A to 3D, the inner components at distal end 102of apparatus 100 are illustrated. FIGS. 3A and 3B respectivelyillustrate distal end 102 in the engaged position of FIGS. 1A and 2A andthe disengaged position of FIGS. 1B and 2B. As shown in FIG. 3A,catheter 104 and cover tube 124 comprise lumens 126 and 128,respectively, for housing the inner components. Latching legs 112 and114 share common ramp portion 130 having inner section 132 and outersection 134 while latching leg 116 has separate ramp portion 136 havinginner section 138 and outer section 140. Inner sections 132 and 138 areangled so as to be positioned closer to the central axis of catheter 104and cover tube 124 relative to the positions of outer sections 134 and140. Latching legs may also include jogs and protrusions. For example,latching leg 116 illustratively includes protrusion 142 proximal to rampportion 136, and jog 144 between hook portion 122 and ramp portion 136.Protrusion 142 is configured to contact the distal surface of annularmember 148 to maintain suitable positioning of latching leg 116. Jog 144is shaped to prevent release ring 146 from moving too distally.

Release ring 146 is coupled to latching legs 112, 114, and 116. Forexample, latching legs 112, 114, and 116 may be partially disposedwithin release ring 146 as illustrated in FIGS. 3A to 3D. Release ring146 is moveable within cover tube 124. Release ring 146 may be locatedin a first position, e.g., an engaged position, where release ring 146contacts inner sections 132 and 138 of ramp portions 130 and 136 suchthat latching legs 112, 114, and 116 extend radially outward as shown inFIGS. 3A and 3C. Release ring 146 may be moved to a second position,e.g., a disengaged position, where release ring 146 contacts outersections 134 and 140 of ramp portions 130 and 136 such that latchinglegs 112, 114, and 116 move radially inward as shown in FIGS. 3B and 3D.In one embodiment, release ring 146 is configured to move from thesecond position to the first position to load a device of the presentinvention and to move from the first position to the second position torelease the device.

Annular member 148 may be partially disposed in the proximal end ofcover tube 124 and configured to couple cover tube 124 to catheter 104via a suitable coupling mechanism, e.g., teeth 150, ribs. Annular member148 includes lumen 152 sized to accept pull-cord 154 therethrough.

Pull-cord 154 is coupled to release ring 146 and actuation of pull-cord154 moves release ring 146 from the first position shown in FIG. 3A tothe second position shown in FIG. 3B, and vice versa. In a preferredembodiment, pull-cord 154 is coupled to handle 108 such that pull-cord154 is actuated by moving finger grips 110 from a locked position shownin FIG. 1A to an unlocked position shown in FIG. 1B, and vice versa.

Pull-cord 154 may be coupled to release ring 146 via release ring base156. In this embodiment, release ring base 156 is directly coupled torelease ring 146 and pull-cord 154 such that actuation of pull-cord 154moves release ring base 156 to move release ring 146 from the firstposition the second position, and vice versa.

Spring 158 may be coupled to the proximal surface of release ring base156 and the distal surface of annular member 148 such that release ringbase 156 and annular member 148 maintain spring 158 therebetween. Spring158 is configured to bias release ring 146 towards a particular positionsuch as towards the first position as shown in FIG. 3A.

FIGS. 3A and 3C illustrate the components at distal end 102 in anengaged position, where FIG. 3C omits cover tube 124 for clarity. Aspull-cord 154 is actuated, e.g., via handle 108, release ring 146 ismoved, e.g., via release ring base 156, from the engaged position to thedisengaged position shown in FIGS. 3B and 3D, where FIG. 3D omits covertube 124 for clarity. Release ring 146 slides along ramp portions 130and 136 from inner sections 132 and 138 to outer sections 134 and 140such that latching legs 112, 114, and 116 move from being extendedradially outward to being positioned radially inward. As release ring146 moves from the engaged position to the disengaged position, spring158 is compressed and as release ring 146 moves from the disengagedposition to the engaged position, spring 158 is decompressed.

FIG. 4A illustrates the components at distal end 102 of apparatus 100engaged to an exemplary device of the present invention and FIG. 4Billustrates the components disengaged from the exemplary device. Device400 includes rings 402 and struts 404 and may be constructed similar todevices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No.9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler, assigned tothe assignee of the present invention, the entire contents of each ofwhich are incorporated herein by reference. As shown in FIG. 4A,latching legs 112, 114, and 116 are sized, shaped, angled, and spacedapart from one another so as to engage device 400 in openings betweenrings 402 and struts 404 when device 400 is in a contracted, deliverystate. Hook portions 118, 120, and 122 are sized, shaped, and angled tofit between rings 402 and struts 404. Hook portions 118, 120, 122 alsohook outwardly away from the center axis at the distal end of thedelivery apparatus. Accordingly, hook portions 118, 120, 122 may bedisposed in the lumen of device 400 in the engaged position of FIG. 4Aand engage device 400 from within the inner surface of device 400 suchthat hook portions 118, 120, 122 extend radially beyond the innersurface of device 400. For example, hook portions 118, 120, 122 mayextend radially to the outer surface of device 400 or beyond the outersurface of device 400. As shown in FIG. 4B, latching legs 112, 114, and116 are configured to move radially inward a sufficient distance todecouple hook portions 118, 120, and 122 from device 400 in thedisengaged position, thereby releasing device 400 for implantation.

FIG. 5 is a flowchart of exemplary method 500 of delivering device 400illustrated in FIGS. 4A and 4B to reduce left atrial pressure in asubject, for example, a human having CHF, using apparatus 100illustrated in FIGS. 1A-1B. Some of the steps of method 500 may befurther elaborated by referring to FIGS. 6A-6Q.

Referring to FIG. 5, first, a device and apparatus for delivering thedevice are provided (step 501). The device may be an hourglass-shapeddevice having a plurality of sinusoidal rings connected bylongitudinally extending struts that define first and second flared endregions and a neck disposed therebetween, as well as an optional tissuevalve coupled to the second flared end region.

Then, the device is collapsed radially to a contracted, delivery stateand coupled to the delivery apparatus (step 502). For example, asillustrated in FIGS. 6A-6C, device 400 may be loaded into taperedloading tube 600 by first placing device 400 within wide diameter end602 of loading tube 600 as shown in FIG. 6A. Then, using loading tool604, device 400 is crimped down within loading tube 600. Loading tool604 includes thin leg end 606 having two thin legs and wide leg end 608having two wide legs. Device 400 may be pushed into loading tube 600first by thin leg end 606 as illustrated in FIG. 6B and then pushedfurther into loading tube 600 by wide leg end 608 as illustrated in FIG.6C. As will be understood by a person ordinarily skilled in the art,thin leg end 606 may have more than two thin legs, e.g., three, four, ormore thin legs, and accordingly, wide leg end 608 may have more than twowide legs, e.g., three, four, or more wide legs.

In FIG. 6D, device 400 is disposed within thin diameter end 610 ofloading tube 600. Thin diameter end 610 has a suitable internal diameterfor contracting the device, e.g., approximately 14 Fr. Loading tube 600includes tapered section 612 between wide diameter end 602 and thindiameter end 610. Tapered section 612 facilitates radial compression ofdevice 400 into thin diameter end 610. Loading tube 600 is coupled toloading cartridge 614 via coupling section 616 having a suitablecoupling mechanism, e.g., threads, ribs. Loading cartridge 614 may betransparent and has a suitable internal diameter, e.g., approximately 14Fr.

Referring to FIG. 6E, device 400 is pushed into loading cartridge 614using pusher 618. Pusher 618 has a suitable diameter, e.g.,approximately 14 Fr., and may have a “star”-shaped end (not shown). Inaccordance with one aspect of the invention, the thin leg end of loadingtool 604 is long enough to serve as pusher 618. Loading cartridge 614 isdisconnected from loading tube 600 and connected to hemostasis valvesection 620, which may be a Tuohy-Borst valve, as shown in FIG. 6F.Valve section 620 includes knob 622 and Y-connector 624. Distal end 102of apparatus 100 is inserted through knob 622 of valve section 620. Knob622 and Y-connector 624 are adjusted to permit movement of apparatus 100while maintaining a seal to prevent fluid leakage, e.g., air leakage,blood leakage. The steps shown in FIGS. 6A-6F may be performed whiledevice 400 is immersed in an anticoagulant such as heparinized saline.

FIGS. 6G and 6H illustrate coupling device 400 to apparatus 100 atdistal end 102. Distal end 102 is advanced within loading cartridge 614toward device 400. The components of distal end 102 may be in thedisengaged position as illustrated in FIG. 6G. For example, the releasering at distal end 102 may contact an outer section of the ramp portionsof the latching legs such that the latching legs are disposed radiallyinward. Next, distal end 102 is moved longitudinally toward device 400and rotated to align the latching legs with suitable portions of device400, e.g., at openings between struts and rings of device 400. Oncesuitable position is achieved, the components of distal end 102 may moveto the engaged position as illustrated in FIG. 6H. For example, therelease ring may be moved via a pull-cord and handle such that therelease ring contacts an inner section of the ramp portions of thelatching legs so the latching legs extend radially outward. Inaccordance with another aspect of the invention, the release ring may bemoved via a PEEK tube as described in further detail below. A medicalprofessional, e.g., a clinician, may verify that device 400 is engagedto apparatus 100 by slowing advancing and retracting apparatus 100 adistance, e.g., approximately 5 mm, while device 400 remains in loadingcartridge 614. In addition, a clinician may verify that apparatus 100 iscapable of disengaging from device 400 within loading cartridge 614 bypressing handle to cause the components at distal end 102 to disengageand then moving distal end 102 away from device 400. After suchverification, the clinician may reengage apparatus 100 to device 400.Preferably, device 400 is loaded into loading cartridge 614 shortlybefore implantation, so as to avoid unnecessarily compressing device 400or re-setting of the optional closed shape of leaflets, which mayinterfere with later deployment or operation of the device.

Referring back to FIG. 5, the device then is implanted, first byidentifying the fossa ovalis of the heart septum, across which device400 is to be deployed (step 503). Specifically, a trans-septal puncturedevice, e.g., a mechanical needle such as a BROCKENBROUGH needle or aradiofrequency trans-septal puncture device, may be percutaneouslyintroduced into the right atrium via the subject's venous vasculature,for example, via the femoral artery. Then, under fluoroscopic and/orechocardiographic visualization, the needle is pressed against the fossaovalis, at a pressure insufficient to puncture the fossa ovalis. Thepressure from the needle causes “tenting” of the fossa ovalis, i.e.,causes the fossa ovalis to stretch into the left atrium. Other portionsof the atrial septum are thick and muscular, and so do not stretch tothe same extent as the fossa ovalis. Thus, by visualizing the extent towhich different portions of the atrial septum tents under pressure fromthe needle, the fossa ovalis may be identified, and in particular, thecentral portion of the fossa ovalis may be located.

The fossa ovalis (particularly its central region) may be punctured withthe trans-septal puncture device, and a guidewire may be insertedthrough the puncture by threading the guidewire through the needle intothe left atrium, and then removing the needle (step 504). The puncturethrough the fossa ovalis then may be expanded by advancing a dilatorover the guidewire through the puncture (step 505). Alternatively, adilator may be advanced over the trans-septal puncture device, withoutthe need for a guidewire. The dilator is used to further dilate thepuncture and a sheath then is advanced over the dilator and through thefossa ovalis; the dilator and guidewire or needle then are removed. Thesheath, which may be 14 Fr., is then flushed.

Distal end 102 of apparatus 100, with device 400 coupled thereto in acontracted, delivery state, then is advanced into the sheath (step 506).For example, the delivery system may be flushed, e.g., via fluidconnected to fluid tube 630, and then loading cartridge 614 may becoupled to sheath 626, e.g., via port 628, as illustrated in FIG. 6I.The clinician should verify that loading cartridge contains no airtherein. In accordance with another aspect of the invention, a TuohyBorst adapter having a Luer fitting may be used which allows forcontinuous flushing of the loading cartridge during connection of theloading cartridge to the hemostasis valve of the delivery sheath. Next,while holding sheath 626 in place, loading cartridge 614 is advanceddistally within port 628 as illustrated in FIG. 6J. The device anddelivery apparatus are advanced distally in sheath 626 until proximalend 106 of apparatus 100 is a predetermined distance X, e.g.,approximately 1 cm, from knob 622 as illustrated in FIG. 6K. Thedelivery system again may be flushed, e.g., via fluid connected to fluidtube 630. The engagement of the latching legs of apparatus 100 withdevice 400 permit movement of device 400 longitudinally forward andlongitudinally backward through sheath 626.

Then, under fluoroscopic and/or echocardiographic visualization, sheath626 may be repositioned such that the distal tip of sheath 626 isdisposed a predetermined distance, e.g., approximately 1-2 cm, distal tothe fossa ovalis within the left atrium. Next, device 400 and apparatus100 are advanced distally such that the device is partially advanced outof the sheath so the first flared end of the device protrudes out of thesheath and into the left atrium, and expands to its deployed state (step507). For example, device 400 and apparatus 100 may be advanced distallyuntil the handle at proximal end 106 contacts knob 622 as shown in FIG.6L. In a preferred embodiment, the distance between proximal end 106 anddistal end 102 of delivery device 100 is adjustable such that only thefirst flared end of shunt device 400 protrudes out of the sheath whenthe handle at proximal end 106 contacts knob 622. Such advancementcauses device 400 to partially protrude out of sheath 626 and into leftatrium LA, which causes the first flared end region to expand in theleft atrium LA, as shown in FIG. 6M. The first flared end region ofdevice 400 may protrude beyond the atrial septum AS into left atrium LAsuch that the angle θ between center axis 628 of device 400, sheath 626,apparatus 100, and/or catheter 104 and the outer surface of the atrialseptum at the left atrial side below device 400 is generallyperpendicular, e.g., between about 80 and about 100 degrees, betweenabout 85 and about 95 degrees, or about 90 degrees, as shown in FIG. 6M.Alternatively, device 400 may be positioned across the atrial septum AS,e.g., across a puncture through the fossa ovalis, at a non-perpendicularangle between center axis 628 and the outer wall of the atrial septum atthe left atrial side below device 400. For example, the angle θ′ may besubstantially greater than 90 degrees as shown in FIG. 6N. Such an anglemay be appropriate when device 400, sheath 626, apparatus 100, and/orcatheter 104 are advanced toward the atrial septum transapically orthrough the inferior vena cava. Exemplary angles θ′ between center axis628 and the outer surface of the atrial septum below device 400 includebetween about 110 and about 170 degrees, between about 120 and about 50degrees, between about 130 and about 150 degrees about 120 degrees,about 125 degrees, about 130 degrees, about 135 degrees, about 140degrees, about 145 degrees, about 150 degrees, about 155 degrees, about160 degrees, about 165 degrees, and about 170 degrees.

As another example, the angle θ″ may be substantially less than 90degrees as shown in FIG. 6O. Such an angle may be appropriate whendevice 400, sheath 626, apparatus 100, and/or catheter 104 are advancedtoward the atrial septum through the superior vena cava. Exemplaryangles θ″ between center axis 628 and the outer surface of the atrialseptum at the left atrial side below device 400 include between about 10and about 70 degrees, between about 20 and about 60 degrees, betweenabout 30 and about 50 degrees, about 10 degrees, about 15 degrees, about20 degrees, about 25 degrees, about 30 degrees, about 35 degrees, about40 degrees, about 45 degrees, about 50 degrees, about 55 degrees, about60 degrees, about 65 degrees, and about 70 degrees.

An hourglass shape may aid in non-perpendicular deployment because theflared ends of the device engage the atrial septum, even when positionedat an angle relative to the central axis of the puncture through theatrial septum.

Next, under fluoroscopic and/or echocardiographic visualization, it isverified that the first flared end of the device protrudes from sheath626 and then knob 622 of Tuohy-Borst connector 620 is used to lock thedelivery system in place within the sheath 626. Sheath 626, along withthe delivery system 100 are pulled proximally causing the first flaredend region of device 400 to engage the left side of the atrial septum ASas shown in FIG. 6M. For example, as the latching legs of apparatus 100are engaged with device 400 within sheath 626, device 400 is preventedfrom accidental deployment wholly within the left atrium LA, which mayalso assist in positioning the device when advanced at non-perpendicularangles as described in FIGS. 6N and 60.

Using fluoroscopic and/or echocardiographic visualization, the cliniciannext verifies that the device is positioned across the fossa ovalis. Theclinician then reduces the pulling force of the sheath and allows thefossa ovalis to straighten. Then, while holding sheath 626 in place,knob 622 is released and the components at distal end 102 of apparatus100 are moved from an engaged position to a disengaged position, e.g.,by actuating handle 108 as shown in FIG. 6P. Then, apparatus 100 ispulled proximally with the sheath 626 a predetermined distance, e.g.,approximately 5-6 cm.

The shunt device then may be fully deployed by pulling the sheathproximally causing the first flared end region to engage the left sideof the atrial septum and the neck of the device to lodge in the puncturethrough the fossa ovalis, and allowing expansion of the second flaredend of the device into the right atrium as shown in FIG. 6Q (step 508).Any remaining components of the delivery system then may be removed,e.g., sheath and distal end of delivery apparatus (step 509). Oncepositioned in the fossa ovalis, the device shunts blood from the leftatrium to the right atrium when the left atrial pressure exceeds theright atrial pressure (step 510), thus facilitating treatment and/or theamelioration of symptoms associated with CHF.

Referring to FIGS. 7A and 7B, an alternative exemplary apparatus isprovided for delivering interatrial shunt devices, e.g., device 400 ofFIGS. 4A and 4B, and/or devices described in U.S. Pat. No. 9,629,715 toNitzan, U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403to Eigler. Apparatus 700 includes distal end 702, catheter 704, proximalend 706, and knob system 703. Distal end 702 comprises componentssuitable for coupling apparatus 700 to devices of the present invention,as described in detail below. Catheter 704 comprises a biocompatibletube shaft of suitable size, e.g., approximately 14 Fr., and suitablelength, e.g., approximately 75-100 cm and preferably 85 cm. Proximal end706 includes handle 708 that is designed to be manipulated, e.g., by ahuman hand, to transition components in distal end 702 from an engagedposition to a disengaged position. In addition, apparatus 700 includesLuer connector 705 in communication with control tube 707 extending fromproximal end 706 to distal end 702 of apparatus 100. For example,control tube 707 may extend through catheter 704 and through handle 708for over-the-wire flushing, e.g., via a Tuohy Borst adapter connected toapparatus 700. Control tube 707 has a lumen extending therethrough sizedto receive a guidewire.

Like handle 108, handle 708 may be manipulated, for example, by movingfinger grips 710 proximally from a locked position shown to an unlockedposition. In addition, handle 708 may be manipulated by moving fingergrips 710 distally from the locked position to the unlocked position soas to transition components in distal end 702 from the disengagedposition to the engaged position to load devices of the presentinvention. Handle 708 also may include securement mechanism 709 coupledto handle safety lock 711 such that finger grips 710 cannot be moveduntil handle safety lock 711 is released. Upon activation, handle 708 isretained in position, enabling a single user to perform the procedure.

FIGS. 8A and 8B illustrate distal end 702 in the engaged position andthe disengaged position, respectively. At distal end 702, apparatus 700may include latching legs 712, 714, and 716 having hook portions 718,720, and 722, respectively. Latching legs 712, 714, and 716 comprise abiocompatible material such as a biocompatible metal or polymer, and arepositioned longitudinally and radially so as to firmly secure devices ofthe present invention for delivery. Hook portions 718, 720, and 722extend outwardly from the distal end of latching legs 712, 714, and 716,respectively, and are configured to fit securely between struts andrings of the devices of the present invention. Preferably, hook portions718, 720, and 722 hook outwardly away from center axis 723 of catheter704 in both the engaged and disengaged positions as shown in FIGS. 8Aand 8B. Center axis 723 is centered relative to catheter 704 on both alongitudinal and cross-sectional basis. By facing outwardly from centeraxis 723, hook portions 718, 720, and 722 may engage the inner surfaceof the device, e.g., within a lumen of a shunt.

In one embodiment, hook portions 718, 720, and 722 move generallyradially away from center axis 723. The angle between the lower surfaceof the hook portion and the longitudinal axis of the latching leg ispreferably less than 90 degrees and greater than 75 degrees, e.g., 87degrees, as shown in FIG. 8C to enable a more secure engagement with theshunt. For example, an angle less than 75 degrees could result infailure to disengage the shunt from the delivery device afterdeployment, whereas an angle greater than 90 degrees could result infailure to achieve half-way retrieval of the shunt by the deliverydevice. Such improved engagement allows the delivery device to pull thedistal flange of a half-deployed shunt back into the sheath(“halfway-retrieval”) in the event the shunt's distal flange is deployedin an undesired location. As will be readily understood by one ofordinary skill in the art, while three latching legs are illustrated,more or fewer latching legs may be used without departing from the scopeof the present invention. For example, one, two, four, five, six, ormore latching legs may be used.

Catheter 704 may include cover tube 724 which may have a larger diameterthan the remaining shaft of catheter 704. Cover tube 724 comprises abiocompatible material such as a biocompatible metal or polymer, and maybe the same or different material than the remaining shaft of catheter704. Components at distal end 702, such as latching legs 712, 714, and716, may be at least partially disposed within cover tube 724. Referringback to FIGS. 8A and 8B, distal end 702 includes control tube 707, e.g.,a polyether ether ketone (PEEK) tube, having a lumen extendingtherethrough sized to receive a guidewire, as described in more detailbelow. Control tube 707 is moveable between an engaged position, wherethe distal end of control tube 707 extends past the distal end of covertube 724 as shown in FIG. 8A, and a disengaged position, where thedistal end of control tube 707 is moved proximally, but still extendspast the distal end of cover tube 724 as shown in FIG. 8B.

Referring now to FIGS. 9A to 9D, the inner components at distal end 702of apparatus 700 are described. FIGS. 9A and 9B respectively illustratedistal end 702 in the engaged position of FIG. 8A and the disengagedposition of FIG. 8B, respectively. As shown in FIG. 9A, catheter 704 andcover tube 724 comprise lumens 726 and 728, respectively, for housingthe inner components. Latching legs 712 and 714 share common rampportion 730 having inner section 732 and outer section 734 whilelatching leg 716 has separate ramp portion 736 having inner section 738and outer section 740. Inner sections 732 and 738 are angled so as to bepositioned closer to central axis 723 of catheter 704 and cover tube 724relative to the positions of outer sections 734 and 740. Latching legsmay also include jogs and protrusions. For example, latching leg 716illustratively includes protrusion 742 proximal to ramp portion 736, andjog 744 between hook portion 722 and ramp portion 736. Protrusion 742 isconfigured to contact the distal surface of annular member 748 tomaintain suitable positioning of latching leg 716. Jog 744 is shaped toprevent release ring 746 from moving too far distally.

Release ring 746 is coupled to latching legs 712, 714, and 716. Forexample, latching legs 712, 714, and 716 may be partially disposedwithin release ring 746 as illustrated in FIGS. 9A to 9D. Release ring746 is moveable within cover tube 724. Release ring 746 may be locatedin a first position, e.g., an engaged position, where release ring 746contacts inner sections 732 and 738 of ramp portions 730 and 736 suchthat latching legs 712, 714, and 716 extend radially outward as shown inFIGS. 9A and 9C. Release ring 746 may be moved to a second position,e.g., a disengaged position, where release ring 746 contacts outersections 734 and 740 of ramp portions 730 and 736 such that latchinglegs 712, 714, and 716 move radially inward as shown in FIGS. 9B and 9D.In one embodiment, release ring 746 is configured to move from thesecond position to the first position to load a device of the presentinvention and to move from the first position to the second position torelease the device.

Annular member 748 may be partially disposed in the proximal end ofcover tube 724 and configured to couple cover tube 724 to catheter 704via a suitable coupling mechanism, e.g., teeth 750, ribs. Annular member748 includes lumen 752 sized to accept control tube 707 therethrough.

Control tube 707 is coupled to release ring 746 and actuation of controltube 707 moves release ring 746 from the first position shown in FIG. 9Ato the second position shown in FIG. 9B, and vice versa. In a preferredembodiment, control tube 707 is coupled to handle 708 such that controltube 707 is actuated by moving finger grips 710 from a locked positionto an unlocked position, and vice versa. In addition, control tube 707includes lumen 755 extending therethrough sized to receive a guidewiresuch that distal end 702 of apparatus 700 may be advanced over aguidewire to the desired device deployment location. The over-the-wirecapability enables safe retrieval of a fully embolized device.

Control tube 707 may be coupled to release ring 746 via release ringbase 756. In this embodiment, release ring base 756 is directly coupledto release ring 746 and control tube 707 such that actuation of controltube 707 moves release ring base 756 to move release ring 746 from thefirst position the second position, and vice versa.

Spring 758 may be coupled to the proximal surface of release ring base756 and the distal surface of annular member 748 such that release ringbase 756 and annular member 748 maintain spring 758 therebetween. Spring758 is configured to bias release ring 746 towards a particular positionsuch as towards the first position as shown in FIG. 9A.

FIGS. 9A and 9C illustrate the components at distal end 702 in anengaged position, where FIG. 9C omits cover tube 724 for clarity. Ascontrol tube 707 is actuated, e.g., via handle 708, release ring 746 ismoved, e.g., via release ring base 756, from the engaged position to thedisengaged position shown in FIGS. 9B and 9D, where FIG. 9D omits covertube 724 for clarity. Release ring 746 slides along ramp portions 730and 736 from inner sections 732 and 738 to outer sections 734 and 740such that latching legs 712, 714, and 716 move from being extendedradially outward to being positioned radially inward. As release ring746 moves from the engaged position to the disengaged position, spring758 is compressed and as release ring 746 moves from the disengagedposition to the engaged position, spring 758 is decompressed.

FIG. 10A illustrates the components at distal end 702 of apparatus 700engaged to an exemplary interatrial shunt device and FIG. 10Billustrates the components disengaged from the exemplary device. Device400 includes rings 402 and struts 404 and may be constructed similar todevices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S. Pat. No.9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler. As shown inFIG. 10A, latching legs 712, 714, and 716 are sized, shaped, angled, andspaced apart from one another so as to engage device 400 in openingsbetween rings 402 and struts 404 when device 400 is in a contracted,delivery state. Hook portions 718, 720, and 722 also are sized, shaped,and angled to fit between rings 402 and struts 404 and hook portions718, 720, 722 hook outwardly away from the center axis at the distal endof the delivery apparatus such that hook portions 718, 720, 722 aredisposed in the lumen of device 400 in the engaged position of FIG. 10Aand engage at the inner surface of device 400. Preferably, hook portions718, 720, and 722 move radially away from center axis 723 at an angleless than 90 degrees, e.g., 87 degrees, toward proximal end 706 ofapparatus 700 as shown in FIG. 8C to enable halfway retrieval of apartially deployed device. As shown in FIG. 10B, latching legs 712, 714,and 716 are configured to move radially inward a sufficient distance todecouple hook portions 718, 720, and 722 from device 400 in thedisengaged position, thereby releasing device 400 for implantation.

FIG. 11 is a flowchart of exemplary method 1100 of delivering device 400to reduce left atrial pressure in a subject, for example, a human havinga heart condition, using apparatus 700 illustrated in FIGS. 7A and 7B.Steps 1101-1104 are similar to steps 501-504 described in FIG. 5, exceptthat apparatus 700 is used instead of apparatus 100, and for brevity arenot discussed again here. At step 1105, a dilator having a guidewirelumen sized and shaped to receive the guidewire therethrough is advancedover the guidewire across the atrial septum through the fossa ovalisinto the left atrium. A sheath is then advanced over the dilator acrossthe atrial septum through the fossa ovalis into the left atrium. Thedilator is then removed. In accordance with another aspect of thepresent invention, a sheath having a dilator disposed therein may beadvanced together over the guidewire across the atrial septum throughthe fossa ovalis into the left atrium.

At step 1106, distal end 702 of apparatus 700, with device 400 coupledthereto, is advanced through the sheath over the guidewire untilproximal end 706 of apparatus 700 is a predetermined distance from theproximal end of the sheath such that distal end 702 of apparatus 700 isa predetermined distance from the distal end of the sheath. Theguidewire is received from the Luer connector 705 via lumen 755 ofcontrol tube 707. Steps 1107-1110 are similar to steps 507-510 describedin FIG. 5, except that apparatus 700 is used instead of apparatus 100and the guidewire may be removed through Luer connector 705 at step1109, and for brevity are not described again herein. Thus, for example,the components at distal end 702 of apparatus 700, e.g., latching legs712, 714, and 716, are moved from an engaged position to a disengagedposition, e.g., by actuating the handle at proximal end 706 to decouplehook portions 718, 720, and 722 from device 400 in the disengagedposition, before the sheath is retracted to deploy device 400 within theatrial septum.

In accordance with another aspect of the present invention, knob system703 may be used for length adjustment of apparatus 700 relative to thesheath during deployment of device 400 at the atrial septum, e.g., toassist in halfway retrieval of device 400. For example, referring now toFIGS. 12A-12C, knob system 703 includes proximal knob 1202, distal knob1204, and optional lock nut 1206. Referring to FIG. 12A, proximal knob1202 may be pulled proximally to enable rotating distal knob 1204clockwise to assist in “halfway retrieval” of device 400 as describedhere. Distal knob 1204 is rotatable to shorten the distance between theknob 1204 and the distal end 702 of apparatus 700, thus pulling distalend 702 proximally within the sheath. For example, in the event that thefirst flared end region of device 400 is deployed and the second flaredend region is still in a collapsed state within the sheath and coupledto distal end 702 of apparatus 700, distal knob 1204 may be rotatedclockwise to retract distal end 702, and thus device 400, within thesheath. As distal end 702 is retracted within the sheath, device 400 isalso retracted, thus causing the first flared end region to collapseinto the sheath.

Referring now to FIGS. 12B and 12C, lock nut 1206 is moveable between anopen and closed position to permit retraction of proximal knob 1202, andthereby rotation of distal knob 1204. Referring to FIG. 12B, lock nut1206 is in an open position such that proximal knob 1202 may be pulledproximally and distal knob 1204 may be rotated to the adjust the lengthof catheter 704 relative to the length of the sheath. When the length ofcatheter 704 relative to the length of the sheath is at the desiredamount, lock nut 1206 may be moved to the closed position as shown inFIG. 12C to fix the set length.

Referring to FIG. 13A, an alternative distal end of an apparatus fordelivering devices of the present invention is provided. Distal end 1302is constructed similar to distal end 102 described in FIGS. 2A to 3D, ordistal end 702 described in FIGS. 8A to 9D, except that distal end 1302includes tube 1304 extending distally from cover tube 1306. Thus, distalend 1302 includes hook portions 1308 and 1310 that move away from acenter axis of the catheter as described above, and tube 1304 includeswindows 1312 and 1314 sized for hook portions 1308 and 1310 to protrudethrough in the engaged position as described in FIGS. 2A, 3A, 3C, 8A,9A, and 9C to engage device 400 in a collapsed state within sheath 1316.As shown in FIG. 13A, when hook portions 1308 and 1310 are in thedisengaged position as described in FIGS. 2B, 3B, 3D, 8B, 9B, and 9D,hook portions 1308 and 1310 do not extend beyond the diameter of tube1304 which prevents the risk of entanglement. As will be readilyunderstood by one of ordinary skill in the art, while two latching legsare illustrated, more or fewer latching legs may be used withoutdeparting from the scope of the present invention. For example, one,three, four, five, six, or more latching legs may be used, andaccordingly, tube 1304 may include a corresponding number of windows.

Referring to FIGS. 13B-13D, an alternative distal end of an apparatusfor delivering devices of the present invention is provided. Distal end1301 is constructed similar to distal end 1302 described in FIG. 13A,and accordingly, distal end 102 described in FIGS. 2A to 3D and/ordistal end 702 described in FIGS. 8A to 9D, except that instead of tube1304, distal end 1301 includes cap 1303 extending distally from covertube 1305. Thus, distal end 1301 includes one or more hook portions 1307that move away from a center axis of the catheter as described above,and cap 1303 includes one or more windows 1309 sized for hook portions1307 to protrude through in the engaged position as described above toengage device 400 in a collapsed state within the sheath. Cap 1303 has arounded surface and is sized and shaped such that when hooks portions1307 are retracted, cap 1303 prevents the shunt from being draggedinward along with hooks portions 1307, insuring that the shunt isreleased. As will be understood by a person having ordinary skill in theart, tube 1304 and cap 1303 may be two separate components coupledtogether or may be formed as a single unitary component.

As described above with regard to, e.g., distal end 102 of FIGS. 2A to3D, hook portions 1307 is coupled to ramp portion 1311 that interactswith release ring 1313 to cause hook portions 1307 to move radiallyinward/outward responsive to the longitudinal position of release ring1313 relative to ramp portion 1311. For example, as shown in FIGS. 13Cand 13D, release ring 1313 is positioned along ramp portion 1311 suchthat hook portions 1307 protrudes out through windows 1309 of cap 1303.As shown in FIG. 13D, the inner surface of cover tube 1305 may includeridge 1317 sized and shaped to prevent release ring 1313 from moving toofar distally within cover tube 1305. Moreover, spring 1317 may causerelease ring 1313 to be pushed against ridge 1317, thereby biasing hookportions 1307 in the engaged positioned, unless actuated by the user.

For example, to engage hook portions 1307 from the shunt device, releasering 1313 may be moved proximally via pull-chord 1315. As release ring1313 slides proximally along ramp portion 1311, hook portions 1317 moveradially inward toward the central axis of the catheter within window1309, to thereby disengage with the shunt device without dragging theshunt device inward and insure that the shunt device is released.

Referring to FIG. 14, an alternative exemplary apparatus is provided fordelivering interatrial shunt devices, e.g., device 400 of FIG. 4A, 4B or6Q, and/or devices described in U.S. Pat. No. 9,629,715 to Nitzan, U.S.Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 to Eigler.Apparatus 1400 includes distal end 1402, catheter 1404, and proximal end1406 having handle 1408 for actuating distal end 1402. Distal end 1402is sized and shaped to be advanced through sheath 1410, which is sizedto extend between distal end 1402 and proximal end 1406 over catheter1404. Apparatus 1400 may include inner catheter 1411 extending fromdistal end 1402 through catheter 1404 and through proximal end 1406,e.g., past the proximal most part as shown. Inner catheter 1411 has alumen sized to receive a guidewire therethrough.

Exemplary method 1500 of delivering device 400 to reduce left atrialpressure in a subject, for example, a human having a heart pathology,using apparatus 1400 illustrated in FIG. 14 will now be described withreference to FIG. 15. Some of the steps of method 1500 may be furtherelaborated by referring to FIGS. 16A-16T. Steps 1501-1507 are similar tosteps 1101-1107 described in FIG. 11, except that apparatus 1400 is usedinstead of apparatus 700, and thus for brevity these steps are notdiscussed again here. FIG. 16A is a perspective view of proximal end1406 of apparatus 1400 and FIG. 16B is a partial cross-sectional viewillustrating internal components. FIGS. 16A and 16B illustrate handle1408 at proximal end 1406 of apparatus 1400 when distal end 1402 havingdevice 400 coupled thereto, and catheter 1404 are advanced over theguidewire and through sheath 1410 across the fossa ovalis (step 1506).Handle 1408 includes first actuator 1422, second actuator 1423, andthird actuator 1424 for actuating the components within the distalregion of sheath 1410 such that the shunt transitions between acontracted delivery state, to a partially expanded state, and then to afully expanded deployed state. First, second, and third actuators 1422,1423, and 1424 may be buttons, switches, levers, touchscreens, or thelike. First, second, and third actuators 1422, 1423, and 1424 may becombined into a single component, two components, or may be more thanthree components.

In addition, handle 1408 includes knob 1401. The inner components ofknob 1401 includes a threaded portion that corresponds with a threadedportion coupled to sheath 1410. Accordingly, as knob 1401 is rotatedabout the longitudinal axis of handle 1408, rotational movement of knob1401 is converted to translational movement of the threaded portioncoupled to sheath 1410 along the longitudinal axis of handle 1408,thereby causing movement of sheath 1410 relative to catheter 1404. Thispermits gradual adjustment of the length of sheath 1410 relative tocatheter 1404, and accordingly halfway-retrieval of device 400 whendevice is halfway deployed as will be described in further detail below.Knob 1401 may not be rotated until third actuator 1424 is moved from alocked position to an unlocked position.

As illustrated in FIG. 16B, third actuator 1424 may be coupled to thirdactuator component 1413 rotatable about the longitudinal axis of handle1408, parallel to inner catheter 1411, between a first, second, andthird position. For example, FIGS. 16A and 16B illustrate third actuator1424 in the first position, such that third actuator 1424 is centeredwithin opening 1433 of the housing of handle 1408. Third actuatorcomponent 1413 may include a toothed pattern along its proximal end forengaging with a corresponding indent along the distal end of actuatorring 1415, wherein actuator ring 1415 is freely rotatable about thelongitudinal axis of handle 1408. As shown in FIG. 16B, there is adefined space between an edge of the tooth of third actuator component1413 and an edge of the indent of actuator ring 1415 when third actuator1424 is in the first position. When third actuator 1424 is moved to thethird position, such that third actuator component 1413 is rotated,e.g., clockwise, about the longitudinal axis of handle 1408, the edge ofthe tooth of third actuator component 1413 engages with the edge of theindent of actuator ring 1415. This prevents actuator ring 1415 fromrotating in an opposite direction, e.g., counter-clockwise, about thelongitudinal axis of handle 1408. Thus, second actuator 1423 and secondactuator component 1417 are also prevented from moving distally withinopening 1435 along the longitudinal axis of handle 1408.

When third actuator 1424 is moved to the second position, such thatthird actuator component 1413 is rotated, e.g., counter-clockwise, aboutthe longitudinal axis of handle 1408, the space between the edge of thetooth of third actuator component 1413 and the edge of the indent ofactuator ring 1415 increases such that actuator ring 1415 is free torotate in the same direction, e.g., counter-clockwise until the edge ofthe indent of actuator ring 1415 engages with the edge of the tooth ofthird actuator component 1413. In addition, third actuator component1413 is operatively coupled to a locking mechanism between innercatheter 1411 and a hub disposed within the distal region of sheath 1410as described in further detail below.

Actuator ring 1415 also may include a grooved pattern along its proximalend for engaging with a corresponding indent along the distal end ofsecond actuator component 1417 coupled to second actuator 1423.Accordingly, the edge of the tooth of third actuator component 1413 mayfurther engage with the indent of actuator ring 1415, to thereby rotateactuator ring 1415 until the groove of actuator ring 1415 engages withthe indent of second actuator component 1417. Second actuator 1423 maybe moveable between a first and second position. For example, FIGS. 16Aand 16B illustrate second actuator 1423 in the first position, such thatfirst actuator 1423 is positioned proximally relative to opening 1435 ofthe housing of handle 1408. Third actuator component 1413, actuator ring1415, and second actuator component 1423 include a lumen sized andshaped to receive first actuator component 1419 coupled to firstactuator 1422. In addition, the lumens of third actuator component 1413and actuator ring 1415 are sized and shaped to permit rotation aboutfirst actuator component 1419, whereas the lumen of second actuatorcomponent 1417 may be sized and shaped such that second actuatorcomponent 1417 is only permitted to move longitudinally along firstactuator component 1419.

First actuator component 1419 is moveable along the longitudinal axis ofhandle 1408, parallel to inner catheter 1411, between a first and secondposition. For example, FIGS. 16A and 16B illustrate first actuator 1422in the first position, such that first actuator 1422 is positioneddistally relative to opening 1437 of the housing of handle 1408. Asillustrated in FIG. 16B, first actuator component 1419 may include oneor more lumens 1421 sized and shaped to receive one or more guiderails1431, such that first actuator component 1419 is moveable between thefirst and second positions along guiderails 1431. One or more guiderails1413 are coupled at one end to second actuator component 1417, andcoupled at an opposite end to pusher plate 1440 disposed at the proximalend of handle 1408, wherein pusher plate 1440 is fixedly coupled to aproximal portion of inner catheter 1411. Accordingly, movement of secondactuator component 1417 from the first position to the second positioncauses pusher plate to move distally within the housing of handle 1408via guiderails 1413, thereby causing inner catheter 1411 to movedistally within the distal region of sheath 1410.

First actuator component 1419 includes a lumen sized and shaped toreceive centering element 1429, wherein centering element 1429 is fixedrelative to handle 1408. First actuator 1422 is further coupled toproximal portion 1427 sized and shaped to move within a lumen ofcentering element 1429. Proximal portion 1427 includes a lumen sized andshaped to receive inner catheter 1411, such that proximal portion 1427is moveable between the first and second positions along inner catheter1411. First actuator 1422 may be moveably coupled to inner catheter 1411via proximal portion 1427, and may include port 1425 for coupling to afluid source to introduce fluid into the guidewire lumen of innercatheter 1411 for flushing. In addition, first actuator component 1419is coupled to sheath 1410 for extending and retracting the distal end ofsheath 1410 as described in further detail below.

FIG. 16C illustrates distal end 1402 having device 400 coupled theretoin a collapsed state and catheter 1404 disposed within the distalportion of sheath 1410 (shown in cross-section for clarity), e.g., in aposition suitable for percutaneous delivery to the left atrium of thepatient. Distal end 1402 includes hub 1412 disposed distal to the distalend of catheter 1404. Hub 1412 may have engagement portion 1428 disposeddistal to ring portion 1426, and a proximal portion that is moveablydisposed within a cavity of catheter 1404 as described in further detailbelow. Ring portion 1426 has a diameter that is equal to or slightlyless than the diameter of the inner wall of sheath 1410 such that hub1412 may move backwards and forwards within sheath 1410. Engagementportion 1428 of hub 1412 has a diameter less than that of ring portion1426, such that device 400 may fit between the outer surface ofengagement portion 1428 and sheath 1410 when device 400 is in acollapsed, delivery state. Engagement portion 1428 may have acylindrical shape and a curved distal end as shown. Hub 1412 is moveablerelative to catheter 1404 within sheath 1410 along an inner catheterdisposed within a lumen extending through hub 1412 and catheter 1404 asdescribed in further detail below. Hub 1412 is releaseably coupled tothe distal end of catheter 1404 via a locking mechanism operativelycoupled to third actuator 1424, such that actuation of third actuator1424 from the first position to the second position causes the lockingmechanism to unlock, thereby decoupling hub 1412 from catheter 1404.

In addition, hub 1412 includes one or more engagers, e.g., protrusions1414 and 1416, extending radially outward from a central axis ofcatheter 1404, such that the one or more engagers are disposedcircumferentially about the outer surface of hub 1412, e.g., atengagement portion 1428, and are configured to fit securely betweenstruts and rings of the interatrial devices for delivery. Thus, each ofthe one or more engagers may be sized to engage device 400 in openingsbetween rings 402 and struts 404 when device 400 is in a contracted,delivery state. For example, the distance from the central axis of hub1412 to the outermost surface of each of the one or more engagers isequal to or slightly less than the inner radius of sheath 1410 so thathub 1412 may be moveable within sheath 1410. The distance from thecentral axis of hub 1412 to the outermost surface of each of the one ormore engagers may be equal to the distance from the central axis of hub1412 to the outer surface of ring portion 1426. Accordingly, device 400may be constrained between the one or more engagers and ring portion1426, and between engagement portion 1428 and sheath 1410 in order toprevent dislodgement or early deployment of device 400 within sheath1410. As shown in FIG. 16C, protrusions 1414 and 1416 engage device 400in openings between rings 402 and struts 404 such that device 400 isconstrained between hub 1412 and the inner wall of sheath 1410 in acontracted, delivery state. As will be readily understood by one ofordinary skill in the art, while two engagers are illustrated, more orfewer engagers may be used without departing from the scope of thepresent invention. For example, one, three, four, five, six, seven,eight, or more engagers may be used.

FIG. 16D is a partial cross-sectional schematic of the deliveryapparatus within the sheath during step 1506, wherein the deliveryapparatus is coupled to device 400, and FIG. 16E illustrates thedelivery apparatus of FIG. 16D with device 400 omitted for clarity. Asshown in FIG. 16D, the distal end of sheath 1410, with the deliveryapparatus disposed therein, is advanced across the atrial septum AS.Protrusions 1414 and 1416 fit securely between struts and rings ofdevice 400 such that device 400 is constrained between protrusions 1414and 1416 and ring portion 1426, and between engagement portion 1428 andsheath 1410. As shown in FIG. 16E, hub 1412 is adjacent to catheter 1404such that proximal portion 1432 of hub 1412 is disposed within cavity1436 of catheter 1404. Cavity 1436 is sized and shaped to receiveproximal portion 1432 of hub 1412 a predetermined distance. Cavity 1436has a larger outer diameter than the outer diameter for the lumen incatheter 1404 that receives inner catheter 1411. Proximal portion 1432is coupled to ring portion 1426 via connector 1434. Hub 1412 may bereleaseably coupled to catheter 1404 via a locking mechanism forengaging catheter 1404 to at least one of ring portion 1426 or proximalportion 1432.

In addition, inner catheter 1411 is disposed within a central lumenextending through hub 1412 and catheter 1404. Inner catheter 1411 mayinclude a stop, e.g., lock ring 1438, fixed at a distal end of innercatheter 1411, wherein lock ring 1438 is sized and shaped to be disposedwithin cavity 1430 of hub 1412. Cavity 1430 may extend through at leasta portion of engagement portion 1428 of hub 1412, or completely throughengagement portion 1428 of hub 1412 and at least a portion of ringportion 1426 of hub 1412. Lock ring 1438 ensures that hub 1412 does notextend beyond a predetermined distance distally along inner catheter1411, and that inner catheter 1411 does not retract beyond thepredetermined distance proximally relative to hub 1412. Inner catheter1411 also may include guidewire lumen 1425 sized and shaped to receive aguidewire therethrough. For example, delivery apparatus 1400 may beadvanced over a guidewire such that the distal end of sheath 1410 havingdistal end 1402 coupled to device 400 disposed therein, is positionedacross the fossa ovalis.

Referring now to FIGS. 16F and 16G, first actuator 1422 is then movedfrom a first initial position to a second position within opening 1437of the housing of handle 1408, which causes distal end 1402 includinginner catheter 1411 and hub 1412 having device 400 coupled thereto, andcatheter 1404 to move relative to sheath 1410. As illustrated in FIG.16G, movement of first actuator 1422 causes first actuator component1419 to move from the first initial position to the second positionthrough the lumens of second actuator component 1417, actuator ring1415, and third actuator component 1413 along guiderail 1431, andproximal portion 1427 to move from the first initial position to thesecond position along inner catheter 1411 within centering element 1429.Specifically, movement of first actuator 1424 from the first initialposition to the second position causes first actuator component 1419operatively coupled to sheath 1410 to move sheath 1410 relative tocatheter 1404, hub 1412, and inner catheter 1411, thereby exposing firstflared end region 401 of device 400 beyond the distal end of sheath 1410such that first flared end region 401 expands to its deployed state inthe left atrium as shown in FIG. 16H (step 1507). According to oneaspect of the invention, actuation of first actuator 1422 may causecatheter 1404, hub 1412, and inner catheter 1411 to be advanced distallywhile sheath 1410 remains stationary with respect to atrial septum AS.

FIG. 16I is a cross-sectional schematic of the delivery apparatus withinthe sheath during step 1507, wherein device 400 is partially deployed,and FIG. 16J illustrates the delivery apparatus of FIG. 16I with device400 omitted for clarity. As shown in FIG. 16I, first flared end region401 of device 400 is deployed in the left atrium of the patient apredetermined distance from the atrial septum AS. Referring to FIG. 16J,the delivery apparatus, e.g., hub 1412 and catheter 1404 moves distallywithin sheath 1410 relative to sheath 1410, such that first flared endregion 401 extends beyond the distal end of sheath 1410 and transitionsfrom a collapsed, delivery state to an expanded, deployed state withinthe left atrium, while the second flared end of device 400 remains in acollapsed, delivery state within the distal end of sheath 1410.

Referring now to FIGS. 16K and 16L, second actuator 1423 may then bemoved from the first initial position to the second position whichcauses second actuator component 1417 to move distally along firstactuator component 1419 within the housing of handle 1408. As secondactuator component 1417 moves distally along first actuator component1419, the distal edge of second actuator component 1417 interacts withthe groove of actuator ring 1415, thereby causing actuator ring 1415 torotate until the indent of actuator ring 1415 engages with the edge ofthe tooth of third actuator component 1413. In addition, movement ofsecond actuator component 1417 from the first initial position to thesecond position causes inner catheter 1411 to move distally relative tohub 1412, catheter 1404, and sheath 1410 via guiderails 1431 and pusherplate 1440 as illustrated in FIG. 16M. Accordingly, the deliveryapparatus, e.g., sheath 1410, inner catheter 1411, catheter 1404, andhub 1412 coupled to device 400, may be pulled proximally until firstflared end region 401 engages the atrial septum from within the leftatrium (step 1508).

FIG. 16N is a cross-sectional schematic of the delivery apparatus withinthe sheath during step 1508, wherein inner catheter 1411 has been moveddistally relative to sheath 1410, hub 1412, and catheter 1404 such thatlock ring 1438 is no longer disposed within cavity 1430 of engagementportion 1428 of hub 1412, and the delivery apparatus is pulledproximally until first flared end region 401 engages the left side ofatrial septum AS. FIG. 16O illustrates the delivery apparatus of FIG.16N with device 400 omitted for clarity. Specifically, FIG. 16Oillustrates sheath 1410, hub 1412, inner catheter 1411, and catheter1404 pulled proximally with respect to atrial septum AS. Usingfluoroscopic or echocardiographic visualization, the clinician nextverifies that the device is positioned across the fossa ovalis. Theclinician then reduces the pulling force of sheath 1410, catheter 1404,and hub 1412, and allows the fossa ovalis to straighten. In accordancewith one aspect of the present invention, the physician may reduceand/or stop the pulling force of the delivery apparatus upon forcefeedback provided by the atrial septum against the delivery apparatus,which indicates that device 400 is properly positioned within theopening of the atrial septum. This may prevent accidentally deployingthe entire device in the left atrium and may assist in positioning thedevice when advanced at non-perpendicular angles.

Referring back to FIG. 16L, third actuator 1424 may then be moved fromthe first initial position to the second position, which causes thirdactuator component 1413 to rotate about first actuator component 1419.The engagement between the tooth of third actuator component 1413 andthe indent of actuator ring 1415 allows rotation of third actuatorcomponent 1413 to rotate actuator ring 1415 in the same direction, e.g.,counter-clockwise, until the groove of actuator ring 1415 engages withthe indent of second actuator component 1417. This causes the lockingmechanism to decouple hub 1412 and catheter 1404 to permit fulldeployment of device 400.

If for any reason device 400 is not in the proper position fordeployment within the atrial septum, sheath 1410 may be advanced overdevice 400 while catheter 1404 is stationary, thereby collapsing firstflared end region 401 within sheath 1410. Specifically, knob 1401 ofhandle 1408 may be rotated to cause sheath 1410 to move translationallyrelative to catheter 1404 and device 400, to thereby collapse device 400within sheath 1410. For example, sheath 1410 may be moved over collapseddevice 400 until device 400 is completely collapsed within sheath 1410.Distal end 1402, with device 400 disposed therein, may then beretrieved. Alternatively, distal end 1402 may be repositioned relativeto the fossa ovalis of the atrial septum prior to partially advancingfirst flared end region 401 out of sheath 1410 within the left atrium.

When third actuator 1424 is in the second position and hub 1412 andcatheter 1404 are decoupled, the delivery apparatus may be pulledproximally by the physician such that the atrial septum maintains device400 in position against the left side of the atrial septum until secondflared end region 403 of device 400 is no longer constrained between hub1412 and sheath 1410 as shown in FIG. 16P. As sheath 1410, catheter1402, and inner catheter 1411 are retracted proximally, hub 1412 remainsstationary with respect to the atrial septum as the one or more engagersof hub 1412 are engaged with the struts of second flared end region 403of device 400 within sheath 1410. Hub 1412 is permitted to move distallyalong inner catheter 1411 until cavity 1430 of hub 1412 prevents lockring 1438 of inner catheter 1411 from further proximal movement. Whensecond flared end region 403 of device 400 is exposed beyond the distalend of sheath 1410, second flared end region 403 then transitions from acollapsed, delivery state to an expanded, deployed state within theright atrium, and neck region 405 is lodged in the puncture of theatrial septum (step 1509).

FIG. 16Q is a cross-sectional schematic of the delivery apparatus withinthe sheath during step 1509, wherein the delivery apparatus is pulledproximally such that second flared end region 403 of device 400 is nolonger constrained between hub 1412 and sheath 1410. FIG. 16Rillustrates the delivery apparatus of FIG. 16Q with device 400 omittedfor clarity. As shown in FIG. 16Q, sheath 1410 is no longer disposedover protrusions 1414 and 1416 such that second flared end region 403 isno longer constrained in the collapsed, delivery state, thereby causingfirst flared end region 401 to engage the left side of the atrial septumand neck region 405 of the device to lodge in the puncture through thefossa ovalis, and allowing expansion of second flared end region 403 ofthe device into the right atrium as shown in FIG. 16S.

Referring back to FIG. 16R, inner catheter 1411, catheter 1404, andsheath 1410 are pulled proximally while hub 1412 of the deliveryapparatus, e.g., engagement portion 1428, ring portion 1426, andproximal portion 1432, remains stationary with respect to atrial septumAS until at least a portion of proximal portion 1432 of hub 1412 is nolonger disposed within cavity 1436 of catheter 1404. In addition, atleast a partial portion of ring lock 1438 of inner catheter 1411 may bedisposed within cavity 1430 of engagement portion 1428 of the hub. Asdescribed above, ring lock 1438 and cavity 1430 prevent inner catheter1411 from being pulled proximally relative to the hub beyond apredetermined distance.

Any remaining components of the delivery system then may be removed,e.g., sheath, distal end of delivery apparatus, the catheter, and theguidewire (step 1510). Once positioned in the fossa ovalis as shown inFIG. 16T, device 400 shunts blood from the left atrium to the rightatrium when the left atrial pressure exceeds the right atrial pressure(step 1511), thus facilitating treatment and/or the amelioration ofsymptoms associated with CHF.

It should be noted that the inventive devices also may be used withpatients having disorders other than heart failure. For example, in oneembodiment the device may be implanted in a subject suffering frommyocardial infarction, for example in the period immediately followingmyocardial infarction (e.g., within a few days of the event, or withintwo weeks of the event, or even within six months of the event). Duringsuch a period, the heart remodels to compensate for reduced myocardialfunction. For some subjects suffering from severe myocardial infarction,such remodeling may cause the function of the left ventricle tosignificantly deteriorate, which may lead to development of heartfailure Implanting an inventive device during the period immediatelyfollowing myocardial infarction may inhibit such deterioration in theleft ventricle by reducing LAP and LVEDP during the remodeling period.The device optionally then may be removed as described in further detailbelow.

Exemplary method 1700 of retrieving device 400 from a subject, forexample, from a puncture through the fossa ovalis, will now be describedwith reference to FIG. 17. The steps of method 1700 may be furtherelaborated by referring to FIGS. 18A-18F.

FIG. 17 is a flow chart of steps in an exemplary method of retrieving anhourglass-shaped device implanted in a puncture through the fossa ovalisin accordance with the present invention. At step 1701, a retrievalsystem for retrieving an implanted shunt device, e.g., hourglass-shapeddevice 400 of FIG. 4, is provided. For example, the retrieval systemincludes a retrieval catheter, e.g., grappling hook, having one or morehook portions at the distal end thereof which preferably are formed of ashape memory metal and are biased toward a position radially outwardfrom a central axis of the retrieval catheter, a restraint membercoupled to a control tube and positioned over at least a portion of theretrieval catheter, and a sheath having a lumen sized and shaped toreceive the retrieval catheter and the restraint member. The hookportions are sized and shaped to align with the openings between thestruts and rings of the shunt device. Accordingly, the number of hookportions may correspond with the number of openings between the strutsand rings of the shunt device.

At step 1702, a guidewire is inserted through the neck of the implantedshunt device through the fossa ovalis of the atrial septum into the leftatrium. The guidewire may be inserted using techniques readily known inthe art. At step 1703, the sheath is inserted over the guidewire andpositioned in proximity to the flared end region of the shunt devicedisposed in right atrium. The guidewire may then be removed. At step1704, the retrieval catheter and the restraint member are deliveredthrough the sheath in proximity to the flared end region of the shuntdevice disposed in right atrium. FIG. 18A is a partial cross-sectionalschematic of retrieval system 1800 during step 1704. As illustrated inFIG. 18A, sheath 1802 having retrieval catheter 1804 and restraintmember 1808 disposed therein is positioned in proximity to second flaredend region 403 of device 400 within the right atrium. Restraint member1808 is positioned over a portion of retrieval catheter 1804 such thathook portions 1806 are maintained in a compressed configuration withinsheath 1802. Although only two hook portions 1806 are illustrated inFIG. 18A, as will be understood by a person ordinarily skilled in theart, retrieval catheter 1804 may include less or more than two hookportions, e.g., one, three, four, five, or six hook portions. Restraintmember 1808 may be moved proximally and distally over retrieval catheter1804 within sheath 1802 via control tube 1810. Alternatively, a controlwire having sufficient stiffness may be used to move restraint member1808 within sheath 1802.

At step 1705, retrieval catheter 1804 along with restraint member 1808are advanced distally and exposed beyond the distal end of sheath 1802within the right atrium such that hook portions 1806 are within at leasta portion of second flared end region 403 of device 400, as illustratedin FIG. 18B. At step 1706, restraint member 1808 is retracted proximallyalong retrieval catheter 1804 within sheath 1802 via control tube 1810.Accordingly, hook portions 1806 expand radially outward from the centralaxis of retrieval catheter 1804 as they are no longer restrained byrestraint member 1808, as illustrated in FIG. 18C. At step 1707,retrieval catheter 1804 may be adjusted to align hook portions 1806 withthe openings between the struts and rings of second flared end region403 of device 400.

At step 1708, while hook portions 1806 are maintained in placed andengaged with second flared end region 403 of device 400, restraintmember 1808 is advanced distally toward hook portions 1806 via controltube 1810, thereby causing hook portions 1806, and accordingly secondflared end region 403, to transition to a compressed configuration, asillustrated in FIG. 18D. Next, at step 1709, sheath 1802 is advanceddistally over retrieval catheter 1804 and device 400, through the atrialseptum AS and into the left atrium, thereby causing first flared endregion 401 of device 400 to transition to a compressed configurationwithin sheath 1802, as illustrated in FIG. 18E. Finally, at step 1710,system 1800 is pulled proximally to remove retrieval system 1800 anddevice 400 from the patient, as illustrated in FIG. 18F.

In accordance with another aspect of the present invention, exemplarymethod 1900 of retrieving device 400 from a subject, for example, from apuncture through the fossa ovalis, will now be described with referenceto FIG. 19. The steps of method 1900 may be further elaborated byreferring to FIGS. 20A-20G.

FIG. 19 is a flow chart of steps in an exemplary method of retrieving anhourglass-shaped device implanted in a puncture through the fossa ovalisin accordance with the present invention. At step 1901, a retrievalsystem for retrieving an implanted shunt device, e.g., hourglass-shapeddevice 400 of FIG. 4, is provided. For example, the retrieval systemincludes grappling hook having one or more hook portions at the distalregion thereof which preferably are formed of a shape memory metal andare biased radially inward toward a central axis of the retrievalsystem, an inflatable balloon catheter, and a sheath having a lumensized and shaped to receive the grappling hook and the inflatableballoon catheter. The one or more curved hooked portions of thegrappling hook are sized and shaped to align with the openings betweenthe struts and rings of the shunt device in an expanded state.Accordingly, the number of hook portions may correspond with the numberof openings between the struts and rings of the shunt device. As will beunderstood by a person ordinarily skilled in the art, the inflatableballoon catheter may be delivered within a separate balloon channelmoveable within the sheath.

At step 1902, a guidewire is inserted through the neck of the implantedshunt device through the fossa ovalis of the atrial septum into the leftatrium. The guidewire may be inserted using techniques readily known inthe art. At step 1903, the sheath is inserted over the guidewire andpositioned in proximity to the flared end region of the shunt devicedisposed in right atrium. At step 1904, the grappling hook and theinflatable balloon catheter are delivered through the sheath over theguidewire in proximity to the flared end region of the shunt devicedisposed in right atrium. FIG. 20A is a partial cross-sectionalschematic of retrieval system 2000 during step 1904. As illustrated inFIG. 20A, sheath 2002 having grappling hook 2004 and inflatable ballooncatheter 2008 in a deflated state disposed therein is positioned inproximity to second flared end region 403 of device 400 within the rightatrium. Although only two hook portions 2006 are illustrated in FIG.20A, as will be understood by a person ordinarily skilled in the art,grappling hook 2004 may include less or more than two hook portions2006, e.g., one, three, four, five, or six hook portions. Hook portions2006 of grappling hook 2004 may be joined together at a proximal regionof grappling hook 2004, e.g., via a ring having a lumen sized and shapedto receive inflatable balloon catheter 2008 such that grappling hook2004 may move proximally or distally over inflatable balloon catheter2008 within sheath 2002.

At step 1905, inflatable balloon catheter 2008 is advanced distally,e.g., over the guidewire (not shown), and exposed beyond the distal endof sheath 2002 within the right atrium in a deflated condition such thatinflatable balloon catheter 2008 is positioned within at least a portionof second flared end region 403 of device 400, as illustrated in FIG.20B. At step 1906, inflatable balloon catheter 2008 is inflated to aninflated state within at least a portion of second flared end region 403and neck region 405 of device 400, as illustrated in FIG. 20C. Forexample, inflatable balloon catheter 2008 may be coupled to a source offluid at its proximal end outside the patient's body for inflation ofinflatable balloon catheter 2008, and may expand to have a diameterequal to the diameter of neck region 405 of device 400. Inflation ofinflatable balloon catheter 2008 aligns retrieval system 2000 withdevice 400.

At step 1907, grappling hook 2004 is advanced distally and exposedbeyond the distal end of sheath 2002 within the right atrium. Asillustrated in FIG. 20D, hook portions 2006 of grappling hook 2004 bendradially outwardly in an expanded state as they move across the surfaceof inflatable balloon catheter 2008 in the inflated state. At step 1908,grappling hook 2004 may be adjusted to align hook portions 2006 with theopenings between the struts and rings of second flared end region 403 ofdevice 400.

At step 1909, while hook portions 2006 are maintained in placed andengaged with second flared end region 403 of device 400, inflatableballoon catheter 2008 is deflated and advanced distally into the leftatrium. Alternatively, inflatable balloon catheter 2008 may be deflatedand removed from the patient's body or deflated and retracted into aballoon channel within sheath 2002. Deflation of inflatable ballooncatheter 2008 causes hook portions 2006 of grappling hook 2004, andaccordingly second flared end region 403, to transition to a compressedconfiguration, as illustrated in FIG. 20E.

Next, at step 1910, sheath 2002 is advanced distally over grappling hook2004, device 400, and inflatable balloon catheter 2008, through theatrial septum AS and into the left atrium, thereby causing first flaredend region 401 of device 400 to transition to a compressed configurationwithin sheath 2002, as illustrated in FIG. 20F. Finally, at step 1911,system 2000 is pulled proximally to remove retrieval system 2000 anddevice 400 from the patient, as illustrated in FIG. 18G.

Referring to FIG. 21A, an alternative exemplary apparatus is providedfor delivering interatrial shunt devices, e.g., device 400 of FIG. 4A,4B or 6Q, and/or devices described in U.S. Pat. No. 9,629,715 to Nitzan,U.S. Pat. No. 9,713,696 to Yacoby, and U.S. Pat. No. 10,076,403 toEigler. Apparatus 2100 includes distal end 2102, catheter 2104, andproximal end 2106 having handle 2108 for actuating distal end 2102.Distal end 2102 is removeably coupled to distal tip 2110 having flexiblepigtail-shaped portion 2112 extending therefrom as illustrated in FIG.21B. Apparatus 2100 may include an engagement apparatus disposed withincatheter 2104 extending from proximal end 2106 to distal end 2102 fordelivery and/or retrieval of the interatrial shunt device. Thecomponents of apparatus 2100 may include a guidewire lumen sized toreceive a guidewire therethrough as described in further detail below.

Referring now to FIG. 22, an exemplary loading tool is provided forloading an exemplary hourglass-shaped interatrial shunt constructed inaccordance with the principles of the present invention into distal end2102 of apparatus 2100. Loading tool 2200 includes proximal loader 2202and distal loader 2204. Proximal loader 2202 and distal loader 2204 maybe constructed from, e.g., injection molding, and made of a transparentplastic material such that loading of device 400 therein may be visibleby the user. Proximal loader 2202 has lumen 2208 extending from proximalend 2201 to distal end 2203 of proximal loader 2202, wherein lumen 2208is sized and shaped to receive device 400 in a collapsed delivery stateas well as distal tip 2110 and catheter 2104 of apparatus 2100. Asillustrated in FIG. 22, lumen 2208 has conical shaped cavity 2206 at itsdistal open end which corresponds to the shape of one of the flared endregions of device 400, e.g., the flared end region configured to bedisposed within the left atrium when device 400 is implanted. Further,cavity 2206 is sized such that device 400 must be inserted into proximalloader 2202 in a specific orientation as will be described in furtherdetail below, thereby ensuring proper loading of device 400 intoapparatus 2100. In addition, distal loader 2204 has cavity 2210 sizedand shaped to receive distal end 2203 of proximal loader 2202.

Exemplary method 2300 of using loading tool 2200 to load device 400 intoapparatus 2100 will now be described with reference to FIG. 23. Some ofthe steps of method 2300 may be further elaborated be referring to FIGS.24A-24F. FIG. 24A illustrates proximal loader 2202, distal loader 2204,the distal components of apparatus 2100, and device 400. As illustratedin FIG. 24A, apparatus 2100 is positioned within proximal loader 2202such that the distal portion of catheter 2104 and engagement apparatus2120 are disposed within lumen 2208, and distal tip 2110 extends beyonddistal end 2203 of proximal loader 2202 (step 2301). As shown in FIG.24A, distal tip 2110 is moveably coupled to catheter 2104 via pull-cord2114. Engagement apparatus 2120 may be constructed similar to deliveryapparatus 100 of FIG. 1A and delivery apparatus 700 of FIG. 7A. Forexample, engagement apparatus 2120 includes latching legs having hookportions which may be controllably transitioned between a disengaged andengaged position for engaging with device 400 in a collapsed deliverystate. Engagement apparatus 2120 is moveably disposed within the lumenof catheter 2104 and may be coupled to the distal end of an innercatheter disposed within catheter 2104.

FIG. 24B illustrates device 400 coupled to distal tip 2110 of apparatus2100 while apparatus 2100 is disposed within lumen 2208 of proximalloader 2202 (step 2302). Specifically, device 400 is inserted overpigtail-shaped portion 2112 to be disposed over distal tip 2110, suchthat the outlet end of second flared end region 403 of device 400 isadjacent to cavity 2206 of proximal loader 2202. Cavity 2206 has a sizeand shape that corresponds to first flared end region 401 in an expandedstate, and which may receive the outlet end of second flared end region403 of device 400 in the expanded state. This ensures that device 400 isproperly loaded into apparatus 2100 as the inlet end of first flared endregion 401 could not be inserted into cavity 2206 of proximal loader2202.

FIG. 24C illustrates proximal loader 2202 having apparatus 2100 coupledto device 400 therein, advanced within cavity 2210 of distal loader 2204(step 2303). Specifically, proximal loader 2202 is advanced withincavity 2210 of distal loader 2204 until first flared end region 401 ofdevice 400 contacts the inner wall of cavity 2210. As proximal loader2202, and accordingly apparatus 2201, are further advanced into cavity2210 of distal loader 2204 (step 2304), second flared end region 403transitions from an expanded stated to a collapsed delivery state withinlumen 2208 of proximal loader 2202 as illustrated in FIG. 24D.Specifically, the conical shape of cavity 2206 of proximal loader 2202causes second flared end region 403 to crimp into the collapsed state asforce is applied to second flared end region 403 by proximal loader2202. In addition, pigtail-shaped portion 2212 and at least a portion ofdistal tip 2110 extend beyond an opening of distal loader 2204. Steps2303 and 2304 may be completed in a single motion.

In accordance with the principles of the present invention, the latchinglegs and hook portions of engagement apparatus 2120 may be actuated tobe in a disengaged position, e.g., contracted inward, before proximalloader 2202 is completely advanced within distal loader 2204 so that theengagement hooks of engagement apparatus 2120 may be appropriatelyaligned with the struts of second flared end region 403 of device 400,and so that second flared end region 403 can smoothly enter lumen 2208of proximal loader 2202. Once aligned, the latching legs and hookportions of engagement apparatus 2120 may be actuated to be in a engagedposition to engage with second flared end region 403 of device 400within lumen 2208 of proximal loader 2202 (step 2305).

FIG. 24E illustrates catheter 2104 advanced further through lumen 2208of proximal loader 2202 over engagement apparatus 2120, device 400, andpull-cord 2114 until the distal end of catheter 2104 engages with distaltip 2110 (step 2306). Specifically, as the distal tip of catheter 2104comes into contact with first flared end region 401, further advancementof catheter 2104 against the outer surface of first flared end region401 cause first flared end region 401 to crimp into a collapsed statewithin the lumen of catheter 2104. The distal end of catheter 2104 maythen be coupled to distal tip 2110 (step 2307). Finally, apparatus 2100having device 400 in a collapsed delivery state therein and engaged withengagement apparatus 2120 within catheter 2104 of apparatus 2100, isremoved from proximal loader 2202 and distal loader 2204 (step 2308).

FIG. 25A illustrates catheter 2104 coupled to distal tip 2110 ofapparatus 2100. As shown in FIG. 25A, apparatus 2100 may includeradiopaque marker 2122 disposed at the distal end of catheter 2104 forassisting in accurate deployment of device 400 within the interatrialseptum. Specifically, as described in further detail below, radiopaquemarker 2122 may be visualized by the physician during the deliveryprocedure to ensure that it is aligned with the atrial septum for properdelivery. FIG. 25B illustrates the components within catheter 2104 withdevice 400 loaded therein. As illustrated in FIG. 25B, collapsed device400 is positioned within catheter 2104 such that one end is engaged withengagement apparatus 2120, and the other end is aligned with radiopaquemarker 2122 so that the neck region of device 400 is a predetermineddistance from radiopaque marker 2122. As described in further detailbelow, knowing where the neck region of device 400 is within catheter2104, by knowing its distance from radiopaque marker 2122 will assist inproper and accurate deployment of device 400 within the fossa ovalis.

FIG. 25C is a cross-sectional view of the distal end of apparatus 2100.As shown in FIG. 25C, apparatus 2100 may include guidewire lumen 2116extending therethrough, e.g., from an opening at the end ofpigtail-shaped portion 2116 through distal tip 2110 and pull-cord 2114to the proximal end of apparatus 2100. Guidewire lumen 2116 is sized andshaped to receive a guidewire so that apparatus 2100 may be advancedover the guidewire across the atrial septum for implantation of device400. In addition, as illustrated in FIG. 25C, engagement apparatus 2120includes hook portions 2118 which may be constructed similar to the hookportions of delivery apparatus 100 of FIG. 1A and delivery apparatus 700of FIG. 7A, for engaging and disengaging device 400 with engagementapparatus 2120.

FIGS. 26A and 26B illustrates handle 2108 coupled to distal end 2106 ofapparatus 2100. As shown in FIG. 26A, handle 2108 includes safetytrigger 2126 and knob 2124. As illustrated in FIG. 26B, knob 2124includes a threaded portion that corresponds with threaded portion ofcatheter component 2127 coupled to catheter 2104. Accordingly, as knob2124 is rotated about the longitudinal axis of handle 2108, rotationalmovement of knob 2124 is converted to translational movement of cathetercomponent 2127 along the longitudinal axis of handle 2108, therebycausing movement of catheter 2104 relative to engagement apparatus 2120.This permits gradual adjustment of the length of catheter 2104 relativeto engagement apparatus 2120, and accordingly halfway-retrieval ofdevice 400 when device is halfway deployed as will be described infurther detail below. Knob 2124 may not be rotated until safety trigger2126 is moved from a locked position to an unlocked position.

Exemplary method 2700 of delivering device 400 to reduce left atrialpressure in a subject, for example, a human having a heart pathology,using apparatus 2100 illustrated in FIG. 21A will now be described withreference to FIG. 27. Some of the steps of method 2700 may be furtherelaborated by referring to FIGS. 28A-28I.

At step 2701, an interatrial shunt, e.g., device 400, and apparatus 2100of FIG. 21A for delivering device 400 are provided. Then, device 400 iscollapsed radially to a contracted delivery state and coupled toapparatus 2100, e.g., using method 2300 of FIG. 23. Steps 2703 and 2704are similar to steps 503 and 504 described in FIG. 5, and thus forbrevity these steps are not discussed again here. FIG. 28A illustratesguidewire 2801 disposed across the atrial septum in left atrium LA (step2704).

Pigtail-shaped portion 2112 of distal tip 2110 of delivery apparatus2100 with device 400 collapsed therein and coupled to engagementapparatus 2120 of apparatus 2100 is then advanced over guidewire 2801through the puncture in the fossa ovalis and into left atrium LA (step2705) as illustrated in FIG. 28B. Next, catheter 2104 is retractedproximally relative to distal tip 2110 and engagement apparatus 2120coupled to collapsed device 400 such that device 400 is partiallyadvanced out of catheter 2104 (step 2706). Such advancement causesdevice 400 to partially protrude out of catheter 2401 and into leftatrium LA, which causes the first flared end region to expand to itsdeployed expanded state in the left atrium LA, as shown in FIG. 28C.

Then, under fluoroscopic and/or echocardiographic visualization,apparatus 2100 may be repositioned such that radiopaque marker 2801 isaligned with the fossa ovalis (step 2707) as illustrated in FIGS. 28Dand 28E. As shown in FIG. 28E, when apparatus 2100 is in the properposition, the neck region of device 400 will be aligned with the fossaovalis for accurate deployment of device 400 within the atrial septum.Thus, device 400 will be loaded to a specific position within catheter2104 of apparatus 2100 relative to radiopaque marker 2122 during method2300 described above.

If for any reason device 400 is not in the proper position fordeployment within the atrial septum, catheter 2104 may be advanced overdevice 400 while distal tip 2110 is stationary, thereby collapsing thefirst flared end region within catheter 2104 (step 2708) as illustratedin FIG. 28F. Specifically, knob 2124 of handle 2108 may be rotated tocause catheter 2104 to move translationally relative to engagementapparatus 2120 and distal tip 2110 of apparatus 2100, to therebycollapse device 400 within catheter 2104. For example, catheter 2104 maybe moved over collapsed device 400 until catheter 2104 engages withdistal tip 2110 as shown in FIG. 28F. Apparatus 2100, with device 400disposed therein, may then be retrieved, e.g., over guidewire 2801 (step2709). Alternatively, apparatus 2100 may be repositioned relative to thefossa ovalis of the atrial septum prior to returning to step 2706 andpartially advancing the first flared end region out of catheter 2104within left atrium LA.

After step 2707 described above, when device 400 is properly positionedrelative to the atrial septum, engagement apparatus 2120 may bedisengaged from device 400, e.g., hook portions 2118 may be moved froman engaged positioned radially inward to a disengaged position. Then,catheter 2104 may be retracted proximally relative to distal tip 2110,causing the second flared end region of device 400 to be exposed withinright atrium RA beyond the distal end of catheter 2104 such that thesecond flared end region transitions from the collapsed delivery stateto an expanded state within right atrium RA (step 2710) as illustratedin FIG. 28G. Specifically, knob 2124 of handle 2108 may be rotated inthe opposite direction to cause catheter 2104 to move translationallyrelative to engagement apparatus 2120 and distal tip 2110 of apparatus2100, to thereby expose the second flared end region of device 400within right atrium RA. Accordingly, the flared end region of device 400will be disposed within left atrium LA, the neck region of device 400will be lodged within the puncture through the fossa ovalis, and thesecond flared end region of device 400 will be disposed within rightatrium RA. In addition, pull-cord 2114 will be positioned within acentral lumen of device 400.

As illustrated in FIG. 28H, which shows device 400 from within rightatrium RA, distal tip 2110 is sized and shaped to fit through thecentral lumen of device 400 in the full expanded state. When device 400is fully expanded within the atrial septum, apparatus 2100 may beretrieved (step 2711) by pulling distal 2100 proximally, e.g., untilcatheter 2104 engages with distal tip 2110 as shown in FIG. 28I.Guidewire 2801 may then be removed. Blood may then be shunted from leftatrium LA to right atrium RA through device 400, e.g., when left atrialpressure exceeds right atrial pressure.

Referring now to FIGS. 29A-29D, an exemplary guidewire loading toolconstructed in accordance with the principles of the present inventionis described. Guidewire loading tool 2900 is designed for use withloading cartridge 614 of FIGS. 6D-6I. Specifically, as illustrated inFIGS. 29A-29D, guidewire loading tool 2900 has proximal portion 2903 anddistal portion 2901, and two flexible wings, e.g., first flexible wing2902 and second flexible wing 2904, coupled to and extending radiallyaway from distal portion 2901. First flexible wing 2902 and secondflexible wing 2904 each have lateral end portions having an edge thatruns parallel to the longitudinal axis of proximal portion 2903 anddistal portion 2901, which permit guidewire loading tool 2900 to beplaced on a flat horizontal surface while a guidewire is loaded thereinas described in further detail below.

In addition, guidewire loading tool 2900 has central lumen 2905extending through proximal portion 2903 and distal portion 2901, sizedand shaped to receive loading cartridge 614 therein, e.g., when device400 is collapsed in a delivery state within loading cartridge 614 asdescribed above with reference to FIG. 6F. Referring again to FIG. 29A,first and second flexible wings 2902 and 2904 are designed such thatwhen a force is applied against first and second flexible wings 2902 and2904 toward each other, the diameter of central lumen 2905 is increasedto permit insertion and removal of loading cartridge 614 therein.Accordingly, first and second flexible wings 2902 and 2904 are biasedtoward an open position whereby central lumen 2905 has a smallerdiameter than when first and second flexible wings 2902 and 2904 arepressed toward each other.

Referring now to FIGS. 30A-30E, an exemplary method of using guidewireloading tool 2900 to load a guidewire is provided. As shown in FIG. 30A,guidewire loading tool 2900 is inserted over loading cartridge 614having device 400 collapsed therein. Specifically, first and secondflexible wings 2902 and 2904 are pressed toward each other to increasethe diameter of central lumen 2905, and loading cartridge 614 ispositioned within central lumen 2905. First and second flexible wingsmay then be released such that loading cartridge 614 is securelydisposed within central lumen 2905 of guidewire loading tool 2900 asillustrated in FIG. 30B.

Next, as illustrated in FIG. 30C, a guidewire is inserted through alumen of device 400 collapsed within loading cartridge 614 disposedwithin central lumen 2905 of guidewire loading tool 2900. The guidewiremay be fed therethrough and extend beyond a proximal end of loadingcartridge 614. As shown in FIG. 30D, when the guidewire is sufficientlyinserted within loading cartridge 614 and guidewire loading tool 2900,first and second flexible wings 2902 and 2904 may be pressed toward eachother to enlarge central lumen 2905. Accordingly, guidewire loading tool2900 may be removed from loading cartridge 614 as shown in FIG. 30E.

Exemplary method 3100 of delivering device 400 to reduce left atrialpressure in a subject, for example, a human having a heart pathologywill now be described with reference to FIG. 27. Some of the steps ofmethod 3100 may be further elaborated by referring to FIGS. 32A-32K.Steps 3101-3104 may be identical to steps 2701-2704 of FIG. 27, andtherefore will not be discussed for brevity. Thus, at step 3104,guidewire 3201 will be positioned across atrial septum AS such that thedistal end of guidewire 3201 is positioned in left atrium LA as shown inFIG. 32A.

At step 3105, the distal end of sheath 3202 having cap 3204 disposedthereon is advanced over guidewire 3201 to a position within rightatrium RA adjacent atrial septum AS, as shown in FIG. 32B. Sheath 3202includes balloon 3206 disposed thereon, proximal to the distal end ofsheath 3202 by a predetermined distance as described in further detailbelow. Accordingly, balloon 3206 may be coupled to a source of fluidexternal to the patient via an inflation lumen disposed either within oralong the exterior of sheath 3202. Cap 3204 may form a seal with thedistal end of sheath 3202 such that fluid cannot leak into or out of thelumen of sheath 3202 during delivery of sheath 3202 to the targetlocation.

At step 3106, balloon 3206 may be inflated via the external fluid sourceand the inflation lumen until balloon 3206 reaches a desired inflatedsize, as shown in FIG. 32C. For example, balloon 3206 may be inflatewith any biocompatible fluid, e.g., saline, water, or air. At step 3107,when balloon 3206 is in its inflated state, the distal end of sheath3202, along with cap 3204, are advanced through the puncture in thefossa ovalis of atrial septum AS until inflated balloon 3206 engages theright side of atrial septum AS from within right atrium RA, as shown inFIG. 32D. The force feedback provided by atrial septum AS againstballoon 3206 informs the physician that the distal end of sheath 3202 isin the desired position within left atrium LA for the next phase ofimplantation of the shunt device. Accordingly, balloon 3206 will bedisposed at a predetermined position along sheath 3202 from the distalend of sheath 3202. Thus, unlike the retention devices described in U.S.Pat. No. 5,312,341 to Turi, inflatable balloon 3206 of the presentinvention is inflated in the right atrium of the patient, proximal tothe atrial septum to prevent sheath 3202 from advancing more than apredetermined distance into the left atrium, allowing for safedeployment of device 400.

At step 3108, cap 3204 may be decoupled from the distal end of sheath3202, and retracted through the lumen of sheath 3202 and removed overguidewire 3201, as shown in FIG. 32E. Referring now to FIG. 31B, at step3109, the distal end of the delivery apparatus having device 400 coupledthereto in a collapsed configured within sheath 3202 may be advancedthrough the lumen of sheath 3202 over guidewire 3201 such that device400 is position within left atrium LA within sheath 3202.

Solely for exemplary purposes, FIGS. 32F-32I illustrate deliveryapparatus 1301 of FIGS. 13B-13D as used to delivery device 400; however,as will be understood by a person having ordinary skill in the art, anyof the delivery apparatuses discussed herein may be used to deliverydevice 400 in accordance with the exemplary steps of method 3100.Accordingly, at step 3110, delivery device 1301 is advanced through thelumen of sheath 3202 until device 400 is partially advanced out of thedistal end of sheath 3202 such that the first flared end region ofdevice 400 is exposed beyond the distal end of sheath 3202 andtransitions from a collapsed delivery state to an expanded deployedstate within left atrium LA, as shown in FIG. 32F. While deliveryapparatus 1301 is being advanced through sheath 3202, the physician maycontinuously or periodically apply a slight forward force on sheath 3202to ensure that force feedback is being observed by the physician due toatrial septum AS and balloon 3206 to ensure that the distal end ofsheath 3202 is appropriately positioned during deployment of device 400.

At step 3111, delivery apparatus 1301 may be disengaged from the secondflared end region of device 400 while the second flared end region is ina collapsed delivery state within sheath 3202 as discussed above. Forexample, the release ring of delivery apparatus 1301 may be retracted,thereby causing the hook portions to move radially inward to disengagewith device 400 within sheath 3202. Once disengaged, delivery apparatus1301 may be retracted and/or completely removed from sheath 3202, asshown in FIG. 32G. At step 3112, sheath 3202 is retracted along withdevice 400 partially disposed therein until the first flared end regionof device 400 engages with the left side of atrial septum AS within leftatrium LA, the neck of device 400 is lodged within the puncture of thefossa ovalis. As sheath 3202 is further retracted, the force of atrialseptum AS against the first flared end region of device 400 causesdevice 400 to be fully exposed from the distal end of sheath 3202 suchthat the second flared end region transitions from the collapseddelivery state within sheath 3202 to the expanded deployed state withinright atrium RA, as shown in FIG. 32H.

At step 3113, balloon 3206 is deflated via the inflation lumen, as shownin FIG. 32I. At step 3114, sheath 3202 and delivery apparatus 1301 maybe retrieved as shown in FIG. 32J, followed by removal of guidewire 3201as shown in FIG. 32K. At step 3115, as described above, blood may beshunted from left atrium LA to right atrium RA through device 400implanted at atrial septum AS, e.g., when left atrial pressure exceedsright atrial pressure.

While various illustrative embodiments of the invention are describedabove, it will be apparent to one skilled in the art that variouschanges and modifications may be made herein without departing from theinvention. It will further be appreciated that the devices describedherein may be implanted in other positions in the heart. For example,device 400 may be implanted in an orientation so as to shunt blood fromthe right atrium to the left atrium, thus decreasing right atrialpressure; such a feature may be useful for treating a high right atrialpressure that occurs in pulmonary hypertension. Similarly, device 400may be implanted across the ventricular septum, in an orientationsuitable to shunt blood from the left ventricle to the right ventricle,or in an orientation suitable to shunt blood from the right ventricle tothe left ventricle. The appended claims are intended to cover all suchchanges and modifications that fall within the true spirit and scope ofthe invention.

1-20. (canceled)
 21. An apparatus for delivering a shunt to an atrialseptum of a patient, the apparatus comprising: a catheter having a lumenand an exterior surface having a first diameter; a cap coupled to adistal end of the cathetere cap comprising an exterior surface having asecond diameter less than the first diameter and one or more windowsdisposed on the exterior surface of the cap; one or more latching legsdisposed within the lumen of the catheter, each of the one or morelatching legs having a hook portion, the one or more latching legsconfigured to move between a first position, where the hook portionprotrudes through the one or more windows of the cap, and a secondposition, where the one or more latching legs move radially inwardwithin the cap to release the shunt; and a pull chord disposed withinthe catheter and configured to move the one or more latching legsbetween the first position and the second position.
 22. The apparatus ofclaim 21, wherein, in the first position, the hook portion protrudesthrough the one or more windows of the cap to a distance equal to orless than the first diameter of the catheter.
 23. The apparatus of claim22, wherein at least a portion of the shunt is pinned between the hookportion in the first position and the exterior surface of the catheterduring delivery of the shunt.
 24. The apparatus of claim 21, wherein thehook portion of the one or more latching legs hooks outwardly away froma center axis of the catheter.
 25. The apparatus of claim 21, whereinthe pull chord is configured to bias the one or more latching legs inthe first position via a spring.
 26. The apparatus of claim 21, whereinthe pull chord is configured to move the one or more latching legsbetween the first position and the second position via a release ringslidably coupled to the one or more latching legs.
 27. The apparatus ofclaim 26, wherein the one or more latching legs has a ramp portiondisposed proximal to the hook portion, and wherein the release ring isconfigured to contact a first section of the ramp portion in the firstposition and to contact a second section of the ramp portion in thesecond position.
 28. The apparatus of claim 21, further comprising: asheath having a distal end and a sheath lumen extending therethrough,the sheath lumen sized and shaped to receive the cap, the catheter, andthe shunt in a collapsed delivery state.
 29. The apparatus of claim 21,wherein the cap comprises a geometry configured to prevent the hookportion of the one or more latching legs from dragging the shunt inwardas the one or more latching legs move from the first position to thesecond position.
 30. The apparatus of claim 28, wherein the sheath isconfigured to be retracted when the one or more latching legs are in thesecond position to thereby fully deploy the shunt at the atrial septum.31. The apparatus of claim 27, wherein the second section of the rampportion is proximal to the first section of the ramp portion.
 32. Theapparatus of claim 28, further comprising a handle operatively coupledto the sheath and the pull chord, wherein the sheath and the pull chordare independently movable responsive to actuation at the handle.
 33. Theapparatus of claim 26, further comprising a ridge disposed on an innersurface of the catheter, the ridge configured to prevent distal movementof the release ring beyond the ridge.
 34. A method for delivering ashunt to an atrial septum of a patient, the method comprising: advancinga distal end of a sheath having a catheter, a cap, and the shunt in acollapsed delivery state disposed therein from a first atrium across theatrial septum to a second atrium, an exterior surface of the cap havinga diameter less than a diameter of the catheter, the cap comprising oneor more windows such that a hook portion of one or more latching legsextends through the one or more windows in a first position to securethe shunt between the hook portion, the catheter, and the sheath;retracting the sheath relative to the shunt, the cap, and the catheterto partially deploy the shunt within the second atrium; moving the oneor more latching legs from the first position through the one or morewindows of the cap to a second position within the cap to disengage theshunt in the collapsed delivery state; retracting the sheath relative tothe shunt, the cap, and the catheter until the shunt is fully deployedwithin the atrial septum; and removing the sheath, the cap, and thecatheter from the patient.
 35. The method of claim 34, furthercomprising advancing a guidewire from the first atrium through theatrial septum into the second atrium, wherein advancing the distal endof the sheath comprises advancing the distal end of the sheath over theguidewire.
 36. The method of claim 34, wherein moving the one or morelatching legs from the first position through the one or more windows ofthe cap to the second position within the cap comprises moving a releasering slidably coupled to the one or more latching legs from a firstsection of a ramp portion of the one or more latching legs to a secondsection of the ramp portion of the one or more latching legs.
 37. Themethod of claim 34, further comprising shunting blood across the atrialseptum through the shunt responsive to pressure difference across theatrial septum.
 38. The method of claim 36, wherein moving the releasering comprises retracting a pull chord coupled to the release ring, thepull chord configured to bias the one or more latching legs in the firstposition via a spring.
 39. The method of claim 34, wherein, in the firstposition, the hook portion protrudes through the one or more windows ofthe cap to a distance equal to or less than the diameter of thecatheter.
 40. The method of claim 34, wherein the hook portion of theone or more latching legs hooks outwardly away from a center axis of thecatheter. 41-48. (canceled)